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CEREBRO-SPINAL    FEVER 


CAMBRIDGE    UNIVERSITY    PRESS 

C.   F.    CLAY,    Manager 

ttoillioil  :   FETTER   LANE,    E.G. 

CUiniuvgf):    loo   PRINCES   STREET 


ILoulioil:    H.  K.  LEWIS  AND   CO.,  Ltd.,  136  GOWER  STREET,  W.C. 

EonUoii:  WILLIAM  WESLEY  AND  SON,  28  ESSEX  STREET,  STRAND 

iacu  gorls:    G.  P.  PUTNAM'S  SONS 

SomlaH,  Calcutta  anB  fHatiras:  MACMILLAN  AND  CO.,  Ltd. 

STorimto:  J.  M.  DENT  AND  SONS,  Ltd. 

CTpiiBO:  THE  MARUZEN-KABUSHIKI-KAISHA 


All  rights  reserved 


CEREBRO-SPINAL    FEVER 


by 
MICHAEL    FOSTER,    M.A.,    M.D. 

Captain   Royal  Army  Medical  Corps,  Territorial  Force 


and 


J.    F.    GASKELL,    M.A.,    M.D. 

Captain   Royal  Army  Medical  Corps,  Territorial  Force 


Cambridge  : 

at   the   University   Press 
1916 


CambtiSgt ; 

PRINTED   BY  JOHN   CLAY,    M.A. 
AT  THE   UNIVERSITY   PRESS 


IN   MEMOKIAM 
M.  F.  W.  H.  G 


Some  will  allow  no  Diseases  to  be  new,  others  think  that 
many  old  ones  are  ceased,  and  that  such  which  are  esteemed 
new,  will  have  but  their  time.  However,  the  Mercy  of  God  hath 
scattered  the  great  heap  of  Diseases,  and  not  loaded  any  one 
Country  with  all:  some  may  be  new  in  one  Country  which 
have  been  old  in  another. 

Sir  Thomas  Bkowue,  A  Letter  to  a  Friend. 


PREFACE 

THIS  book  has  for  its  aim  an  attempt  to  bring  together  and  correlate 
the  clinical  and  pathological  facts  which  we  were  enabled  to 
accumulate  during  the  epidemic  of  1915.  In  January  of  that  year, 
some  of  the  first  cases  to  occur  in  the  Eastern  Command  were  brought 
to  the  1st  Eastern  General  Hospital  for  treatment,  and  came  imder  our 
care.  The  earUer  cases  were  admitted  in  the  first  instance  to  different 
wards  and  were  therefore  under  the  charge  of  various  physicians.  Our 
thanks  are  due  to  Major  Wright  and  Captains  Curl  and  Haynes  for 
allowing  us  every  faciUty  for  stud}dng  the  cases  which  had  been 
admitted  under  their  care.  To  Captain  Curl  we  are  especially  indebted 
for  much  valuable  coimsel  and  help  in  dealing  with  these  earUer  cases. 
At  the  end  of  February  the  War  Office  appointed  one  of  us  bacterio- 
logist to  deal  with  the  outbreak  in  the  Western  part  of  the  Eastern 
Command.  At  the  same  time  Colonel  Griffiths  arranged  that  a  ward 
should  be  set  apart  for  the  treatment  of  all  cases  that  arose.  We  were 
appointed  to  have  charge  of  the  cases  admitted. 

A  laboratory,  which  had  been  equipped  by  the  Insurance  Act 
Committee  for  purposes  of  research  at  the  1st  Eastern  General  Hospital, 
was  given  for  the  investigation.  In  addition  to  providing  the  laboratory, 
the  Committee  assisted  our  investigations  by  appointing  Mr  H.  W.  C. 
Vines  to  study  special  problems  as  they  arose.  We  wish  to  express 
our  great  indebtedness  to  the  Insurance  Act  Committee  for  the  eqxiip- 
ment  so  generously  given.  To  Mr  Vines  our  thanks  are  specially  due 
as  much  of  his  work  has  been  incorporated  in  the  present  volume. 
Major  Hele  also  rendered  valuable  assistance  when  the  pressure  of  work 
was  extremely  great.  In  addition  to  laboratory  work,  it  was  the  duty 
of  the  bacteriologist  to  visit  the  place  of  origin  of  every  case,  and  investi- 
gate the  hygienic  conditions  in  which  it  arose.  At  this  visit  all  contacts 
were  examined  to  discover  carriers.  All  proved  carriers  were  at  once 
brought  into  the  special  Cerebro-Spinal  Fever  ward,  where  they  were 
kept  under  observation  until  two  consecutive  throat  swabs  had  proved 
negative.  Every  case  was  therefore  fully  investigated  by  us  from  its 
commencement  to  the  termination  of  the  illness.     We  have  also  had 


viii  Preface 

the  good  fortune  to  see  several  of  our  cases  some  months  after  their 
discharge  from  hospital. 

The  views  here  set  forth  are  the  outcome  of  cliuical  and  pathological 
observations  made  in  the  wards,  the  laboratory,  and  the  post-mortem 
room  of  the  1st  Eastern  General  Hospital.  Whatever  value  these 
conclusions  may  have,  is  due  to  the  fact  that  the  clinical  and  pathological 
study  of  each  particular  case  was  carried  out  day  by  day  by  the  same 
observers  working  in  conjunction.  It  has  been  claimed  that  the 
epidemic  nature  of  successive  outbreaks  differs  so  essentially  that 
knowledge  gained  in  one  visitation  is  of  but  slight  value  in  another. 
Whether  this  is  the  case  we  have  no  means  of  knowing ;  but  we  would 
point  out  that  the  cases  which  came  under  our  care  supplied  examples 
of  every  variety  of  the  disease  described  in  the  literature  of  the  subject. 

The  method  of  treatment  by  repeated  lumbar  puncture,  which  was 
adopted  in  the  majority  of  cases,  has  rendered  possible  a  study  of  the 
natural  history  of  the  disease  and  the  changes  in  the  cerebro-spinal  fluid, 
unmodified  by  the  operation  of  any  extraneous  agent. 

We  desire  to  express  our  thanks  to  Colonel  Griffiths  for  the 
opportunities  of  studying  the  disease  which  he  has  afforded  us.  We  are 
especially  indebted  to  Major  Apthorpe  Webb  for  his  unfailing  assistance 
in  the  arrangement  and  administration  of  measures  which  often  had  to 
be  evolved  in  face  of  a  sudden  emergency.  To  our  brother  officers  we 
offer  our  grateful  thanks  for  their  constant  help.  The  plates  illustrating 
this  book  were  drawn  by  Mr  West  of  the  Uiiiversity  Press  from  our 
own  cases  and  specimens.  We  are  however  indebted  to  Mr  Vines  for 
the  microscopical  drawing  shown  on  Plate  XI,  fig.  1 .  We  desire  to  thank 
Mr  G.  A.  Harrison,  of  Caius  College,  for  the  photograph  illustrating  head 
retraction.  Owing  to  the  courtesy  of  Messrs  Longman  we  have  been 
allowed  to  introduce  three  anatomical  illustrations  from  Gray's  Anatomy. 
Through  the  kind  offices  of  Professor  Netter,  of  Paris,  and  G.  Steinheil, 
we  have  obtained  permission  to  reproduce  the  figure  of  the  lymphatic 
connections  of  the  sub-arachnoid  space  and  the  upper  part  of  the  nose, 
published  by  M.  le  Docteur  J. -Marc  Andre  in  his  Tliese  de  Paris.  To 
these  gentlemen  we  tender  our  grateful  thanks. 

M.  F. 
J.  F.  G. 

Great  Shelfobd 
January  1,  1916. 


CONTENTS 

CHAP.  PAGE 

I.  Historical      .........  1 

II.  Symptoms        .........  13 

III.  Diagnosis 28 

IV.  Acute  Forms           ....;...  41 

V.  SUB-ACDTE   AND    ChRONIC   CaSES             .....  50 

VI.  Course  and  Prognosis  .    ......  62 

VII.  Treatment 72 

VIII.  Pathology 90 

IX.  Changes  in  the  Ceeebro-spinal  Fluid  and  the  Cultiva- 
tion OF  the  Meningococcus  from  it,  from  the  Blood 
AND  from  the  Urine  .         .         .         .         .         .108 

X.      Epidemiology          ........  119 

XT.     The   Bacteriology  op  the  jVIeningococcus  and   other 

Gram-negative  Diplococci        .....  139 

Plates 169 

Appendix  I     ........         .  191 

Appendix  II    ........         .  196 

Bibliography  and  Index  of  Authors    .         .         .         .198 

General  Index       ........  207 


ILLUSTRATIONS 


PLATES 

{to  follow  page  168) 

I.  The  Macular  Rash 

II.  Fig.  1.     The  Erythematous  Rash 
Fig.  2.     The  Petechial  Rash 

III.  The  Petechial  Rash 

IV.  The  Purpuric  Rash 

V.  Fig.  1.     The  Communications  between  the  Sub-Arachnoid  Space 
and  the  Nose 

Fig.  2.     Head  Retraction 

VI.  Kernig's  Sign 

VII.  Brain  of  an  Acute  Fatal  Case 

VIII.  Brain  of  a  Suppurative  Case 

IX.  Fig.  1.     Brain  of  a  Hydrocephalic  Case 

Pig.  2.  Brain  of  an  Acute  Case  shewing  Early  Hydrocephalus 

Plate  X.      Fig.  1.  Cord  of  an  Acute  Fatal  Case 

Fig.  2.  Cord  of  a>  Suppurative  Case 

Fig.  3.  Cord  of  a  Hydrocephalic  Case 

Fig.  4.  Cord  from  a  Case  of  Meningitis  following  Middle  Ear 
Disease 

Plate  XI.     Fig.  1.  Section  of  Meninges  shewing  Meningococci 

Fig.  2.  Film  from  the  Ccrebro-Spinal  Fluid  in  a  Fulminating  Case 


Plate 
Plate 

Plate 
Plate 
Plate 

Plate 
Plate 
Plate 
Plate 


CHARTS  m  TEXT 

Chart  1.  Influence  of  Lumbar  Puncture  on  Temperature 

Chart  2.  Temperature  in  Fulminating  Case 

Chart  3.  Temperature  in  Acute  Case  with  Recovery 

Chart  4.  Chronic  Fever  simulating  Malaria 

Chart  5.  Temperature  in  a  Chronic  Recrudescent  Case    . 


PAGE 

16 
17 
17 
17 
53 


FIGURES   IN  TEXT 

Fig.  1.     The  Cisternae  of  the  Brain  .         .         .         ... 

Fig.  2.     Dissection  of  the  Membranes  of  the  Cord     . 

Fig.  3.     The  Membranes  of  the  Cord  in  Tran-sverse  Section 


CHAPTER   I 

HISTORICAL 

Nomenclature — First  recorded  appearance  at  Geneva,  HirscKs  four 
•periods.  First  period  :  Geneva,  America,  France.  Second  period : 
Gascony,  Italy,  America.  Third  period :  Sweden,  Germany,  Russia, 
Greece,  Ireland,  America.  Fourth  period :  England,  Cape  Town, 
Poland,  France,  Italy.  Fifth  period  :  Identity  of  Posterior  Basic 
Meningitis  and  Cerebrospinal  Fever  established  ;  France,  America, 
Portugal,  Silesia,  Ireland,  Scotland.  The  English  epidemic  of  1915. 
Outbreaks  in  tropical  countries.  Geographical  distribution.  In- 
fluence of  carriers  and  suitable  conditions. 

Cerebro-spinal  fever  may  be  defined  as  an  infection  of  the  meninges 
caused  by  a  definite  organism,  the  diplococcus  meningitidis  of  Weichsel- 
baum.  The  disease  occurs  in  epidemics,  which  appear  at  varying 
intervals,  and  whose  spread  appears  to  follow  no  definite  path.  Sporadic 
cases  of  this  disease  are  generally  present,  though  in  small  number,  and 
their  identity  with  the  epidemic  form  has  been  established  by  the  most 
rigorous  bacteriological  proof.  This  disease  has  received  many  names, 
in  whose  elaboration  practical  convenience  has  been  sacrificed  to 
attempts  at  scientific  accuracy.  Epidemic  cerebro-spinal  meningitis 
accurately  defines  the  main  features  of  the  disease,  but  is  cumbersome. 
Moreover,  since  every  infection  of  the  brain  by  a  pus-forming 
organism  is  cerebro-spinal  in  character,  owing  to  the  anatomical  re- 
lations of  its  membranes,  the  term  cerebro-spinal  meningitis  appears 
unnecessarily  prolix.  Meningococcal  meningitis  has  been  suggested  by 
Heiman  and  Feldstein.  This  name  has  the  merit  of  accuracy,  but  is 
clumsy  in  use,  and  has  the  further  drawback  that  its  general  adoption 
would  prevent  any  attempt  to  fix  upon  an  adequately  descriptive 
English  name.  The  traditional  names  of  common  diseases  remain  the 
same  through  all  the  chances  and  changes  of  pathological  fashion.  The 
terms  typhus,  typhoid  and  cholera  appear  to  be  immutably  fixed  in 
medical  literature.     The   name   cerebro-spinal   fever  would   seem   to 

F.  &  G.  1 


2  Historical  [ch. 

combine  the  advantage  of  pathological  accuracy  with  popular  con- 
venience. It  has  the  further  merit  that  it  indicates  on  the  one  hand 
the  kinship  of  this  disease  with  the  acute  specific  fevers,  and  on  the 
other  defines  the  essential  pathological  lesion  upon  which  the  symptoms 
depend.  If  it  is  desired  to  draw  attention  to  the  epidemic  nature  of  the 
disease,  the  term  epidemic  meningitis  is  both  accurate  and  descriptive, 
since,  as  has  been  mentioned  above,  the  term  cerebro-spinal  meningitis 
is  redundant.  Various  other  names  have  from  time  to  time  been 
given  to  the  disease :  of  these  the  one  which  has  attained  the  greatest 
measure  of  popularity  is  Spotted  Fever.  This  name,  which  was  given 
to  the  disease  on  its  first  appearance  in  America,  has  the  drawback  that 
it  draws  attention  to  a  far  from  constant  symptom.  In  Italy  the  disease 
is  called  Tifo  Apoplettico.  In  Germany  the  popular  name  Epidemische 
Genickstarre  is  derived  from  another  marked  symptom.  Whether  the 
disease  is  an  entirely  new  one  or  has  always  existed,  is  a  matter  largely 
for  antiquarian  speculation.  Some  authors  think  that  it  can  be  identified 
in  Hippocrates  or  Celsus.  It  would  seem  improbable  that  im.til  the 
last  century  the  disease  was  ever  common  in  these  islands,  if  indeed  it 
ever  reached  them.  Search  has  therefore  revealed  no  description  which 
can  be  identified  with  the  disease  in  the  works  of  Sydenham  or  Huxham. 
It  has  been  conjectured  that  the  petechial  fevers,  references  to  which 
fingered  in  text-books  until  well  into  the  last  century,  may  have  been 
of  this  nature,  but  this  is  a  matter  of  mere  speculation. 

The  first  authentic  account  of  an  epidemic  is  that  which  occurred 
in  Geneva  in  180-5.  This  epidemic  presents  the  singular  feature  that 
both  the  clinical  symptoms  and  morbid  lesions  were  so  well  described 
as  to  establish  once  and  for  all  the  identity  of  the  disease.  The  out- 
break occurred  in  March  1805 ;  the  first  cases  appeared  in  Eaux-Vives, 
a  suburb  on  the  left  bank  of  Lac  Leman ;  others  subsequently  occurred 
at  Paquis  on  the  other  bank  of  the  lake.  The  epidemic  does  not  appear 
to  have  been  particularly  widespread,  since  only  thirty-three  persons 
died  of  the  disease.  The  interest  lies  in  the  contemporary  records. 
Vieusseux  writes :  "  The  initial  symptom  was  a  sudden  failure  of  strength, 
the  expression  was  anxious,  the  pulse  feeble,  sometimes  threadlike,  in 
a  few  cases  hard  and  bounding.  There  was  Adolent  headache,  in  the  main 
frontal.  The  headache  was  followed  by  vomiting  of  green  matter,  by 
stifiness  of  the  spine,  and  in  infants  by  convulsions.  The  body  shewed 
livid  patches  after  death,  occasionally  during  life."  Matthey  has  left 
behind  a  description  of  the  morbid  appearances,  to  which  the  pathologist 
of  to-day  could  have  little  to  add.     "The  vessels  of  the  meninges,"  he 


i]  Historical  3 

says,  "  were  notably  congested.  A  gelatinous  humour  covering  the  brain 
was  markedly  tinged  with  blood.  There  was  fluid  in  the  ventricles. 
The  choroid  plexus  was  of  a  deep  red  colour.  The  base  of  the  brain 
was  covered  by  yellow  puriform  matter,  with  no  obvious  change  in  the 
underlying  cerebral  tissue.  This  exudation  covered  the  optic  chiasma 
and  extended  backwards  towards  the  cerebellum,  reaching  for  the  space 
of  an  inch  down  the  vertebral  canal." 

From  the  date  of  this,  its  first  appearance,  the  disease  was  epidemic 
at  various  places  both  in  Europe  and  America  for  the  next  ten  years. 
Throughout  the  last  century  and  up  to  the  present  day  it  has  been 
epidemic  for  a  few  consecutive  years,  and  quiescent  periods  of  varying 
length  have  then  followed.  Hirsch  has  summarized  these  epidemics  in 
an  exhaustive  and  masterly  article  in  his  Treatise  on  Geographical  and 
Historical  Pathology.  This  author  regards  the  epidemic  prevalence  of 
the  disease  as  grouping  itself  into  four  periods.  The  recent  epi'demics 
both  in  the  Old  and  New  World  constitute  a  fifth  period.  The  periods 
in  Hirsch's  classification  may  be  chronologically  arranged  as  foUows. 
The  first  period  from  1805  to  1815.  The  second  period  from  1837  to  1850. 
The  third  period  from  1854  to  1875.  The  fourth  period  from  1876  to 
1886.  The  fifth  period  may  be  regarded  as  beginning  in  1896  and 
stretching  to  the  present  day.  In  reviewing  the  past  history  of  the 
centres  from  which  outbreaks  spread,  and  the  lines  of  march  along  which 
the  disease  travelled,  its  propagation  appears  at  first  sight  to  follow 
no  appreciable  law.  Read  in  the  light  of  our  present  knowledge,  the 
part  played  by  the  carrier  in  the  propagation  of  the  disease  affords  a 
clear  explanation  of  the  records  of  these  long  past  epidemics.  Assuming 
the  presence  of  a  few  perrnanent  carriers,  it  only  requires  outside  con- 
ditions which  facilitate  the  spread  of  the  organism,  to  create  a  large 
number  of  temporary  carriers.  As  Arkwright  has  remarked,  "The 
number  of  the  carriers  constitutes  the  epidenaic."  The  persons  who  fall 
sick  of  the  disease  are  thus  but  the  concrete  evidences  of  the  wide 
diffusion  of  temporary  carriers.  The  apparently  enigmatical  march  of 
the  disease  in  the  old  epidemics  acquires  a  fresh  interest  and  meaning, 
when  an  attempt  is  made  to  trace  the  path  of  these  long  past  carriers. 
In  reviewing  the  first  epidemic  wave,  its  place  of  origin  may  be  taken 
to  be  at  Geneva  in  March  1805.  Its  next  appearance  was  in  the  New 
World  in  March  1806  at  Medfield  in  the  Commonwealth  of  Massachusetts. 
As  to  whether  any  emigration  from  Switzerland  took  place  there  is 
no  evidence,  but  there  has  always  been  interchange  between  Geneva 
and  North  America.     From  Medfield  the  disease  spread  through  the 

1—2 


4  Historical  [ch. 

New  England  States  of  Connecticut,  Vermont  and  Maine,  where  it 
recurred  in  isolated  epidemics  until  1816.  The  disease  spread  to 
Canada  in  1807,  to  Virginia,  Kentucky  and  Ohio  in  1808,  appearing  in 
the  State  of  New  York  and  in  Pennsylvania  in  1809.  This  American 
epidemic  was  remarkable  for  the  coining  of  the  popular  name  of  spotted 
fever,  by  which  name  it  is  described  in  a  book  entitled  Treatise  on  a 
Malignant  Epideviic  called  Siiotted  Fever,  written  by  North  in  1811. 

In  Europe  the  disease  appeared  amongst  the  Spanish  prisoners  at 
Brian§on  in  1807.  In  1811  it  occurred  at  Dantzig,  then  in  French  occu- 
pation. An  outbreak  occurred  in  the  garrison  at  Grenoble  in  February, 
March  and  April  1814.  The  garrison  of  Paris  was  attacked  during  the 
same  months.  In  the  spring  of  1815  it  occurred  at  Metz  and  Pont  a 
Mousson.  In  the  same  months  an  epidemic  occurred  in  Albenga  and  some 
of  the  surrounding  villages.  This  epidemic  was  of  importance,  since  it  was 
described  by  Sassi  in  1815  under  the  title  Saggio  sulla  spinite  epidemica 
che  ha  regnato  in  Albenga,  and  was  also  described  by  Mela  and  Airaldi. 
It  is  a  matter  for  surprise  that  a  remote  city  on  the  sea-board  of  the 
Ligurian  Alps  should  be  the  seat  of  an  epidemic  confined  apparently 
to  the  valley  in  which  it  stands.  When  viewed  from  the  point  of  view 
of  the  possible  importation  by  carriers,  the  problem  appears  simpler. 
From  Albenga  the  road  leads  up  to  the  main  pass  into  Piedmont,  which 
is  the  only  practicable  one  along  a  stretch  of  momitain  ranges  70  miles 
in  length.  At  the  mouth  of  the  river,  on  which  Albenga  stands,  is  the 
safest  roadstead  between  Nice  and  Genoa,  where  to-day  brigantine  and 
felucca  can  be  seen  sheltering  from  any  sudden  gale.  The  sea-borne 
traffic  was  in  those  days  considerable,  the  coast  road  having  been  a  mule 
path  less  than  twenty  years  before  the  epidemic.  Infection  could  thus 
reach  Albenga  both  by  land  and  sea.  Once  established  the  infection 
might  well  be  limited,  as  every  one  of  the  valleys  bordering  the  shores  of 
the  gulf  of  Genoa  is  a  country  apart  from  its  neighbours,  each  of  them 
to  this  day  presenting  marked  individual  differences  in  dialect. 

From  the  year  1815,  with  the  exception  of  two  small  and  purely  local 
outbreaks  in  America,  the  disease  remained  quiescent  until  the  second 
period,  which  Hirsch  dates  from  1837  to  1850.  The  first  appearance  of  the 
malady  was  in  the  Landes  and  the  valley  of  the  Adour  in  1836.  Ferron, 
who  has  made  an  exhaustive  study  of  the  beginnings  of  this  epidemic 
with  most  interesting  results,  regards  the  place  of  origin  as  Sengresse  in 
the  Landes.  It  was  brought  thither  by  a  Spanish  family  who  had  left 
their  native  country  on  account  of  an  epidemic,  the  nature  of  which 
is  not  recorded.     The  first  person  attacked  was  a  maid-servant,  thirty 


i]  Historical  5 

years  of  age,  who  died  ou  the  15th  of  February  1832.  The  Carlist  war 
then  raging  in  Spain  had  led  to  the  concentration  of  a  large  body  of 
troops  in  this  district.  Such  a  concentration  of  troops,  for  the  most 
part  in  billets,  involves  a  considerable  amount  of  overcrowding.  Further, 
their  mere  presence  and  their  changes  of  station  involve  a  relatively 
larger  shifting  population  than  is  met  with  in  ordinary  civil  life.  The 
conditions  were  therefore  similar  to  those  which  obtained  in  England 
in  the  winter  1914-15.  The  introduction  of  carriers  in  such  circum- 
stances enabled  the  disease  to  estabUsh  itself.  From  the  Landes  the 
contagion  spread  to  the  garrisons  of  Bayonne  and  Dax.  Amongst 
the  troops  quartered  in  the  Landes  at  the  time  of  the  first  outbreak 
were  the  18th  Light  Infantry,  who  were  early  attacked.  They  changed 
quarters  to  Bordeaux,  where  the  disease  continued.  From  Bordeaux 
the  regiment  marched  to  Rochefort,  where  fresh  cases  occurred  in 
January  and  February  1838.  In  the  latter  part  of  this  year  the 
18th  moved  from  Rochefort  to  Versailles.  At  the  latter  station  six 
men  living  in  the  same  room  were  attacked  in  February  1839.  The 
disease  then  spread  through  the  regiment,  and  finally  attacked  the 
whole  garrison.  The  further  wanderings  of  this  regiment  next  brought 
it  to  Chartres,  where  the  disease  again  broke  out.  From  Chartres  the 
18th  moved  successively  to  Metz,  Nancy  and  Strasbourg,  carrying  with 
it  the  infection,  which  soon  manifested  itself  in  the  garrison  of  each 
station.  What  Netter  aptly  terms  the  Odyssey  of  the  18th  regiment 
presents  a  remarkable  record  of  the  human  agencies  which  conveyed 
the  disease  from  the  Pyrenees  to  the  Rhine.  At  the  same  time  that 
the  disease  broke  out  in  the  Landes,  it  also  appeared  at  Narbonne  and 
Foix.  In  the  following  year  it  spread  to  Toulouse,  Nimes  and  Toiilon. 
In  the  winter  of  1839  it  appeared  at  Avignon,  and  in  the  following  winter 
it  spread  from  the  military  to  the  civil  population.  In  1840  it  appeared 
in  Algiers,  a  considerable  number  of  cases  occurring  amongst  the  garrison. 
Marseilles  was  attacked  in  the  winter  of  1841-2,  and  an  outbreak  of 
a  malignant  character  occurred  at  Aigues  Mortes.  The  latter  town,  with 
its  houses  crowded  together  within  the  circuit  of  its  high  surrounding 
walls,  forms  possibly  one  of  the  worst  ventilated  towns  in  the  world, 
so  that  the  gravity  of  the  epidemic  can  hardly  be  a  matter  of  surprise. 
At  the  same  time  as  the  disease  prevailed  in  France,  it  appeared 
also  in  Italy.  The  first  outbreak  occurred  at  Ancona  in  1839;  as 
Netter  points  out,  French  troops  consisting  of  regiments  of  infantry 
and  artillery  had  been  maintained  in  this  city  since  1832.  These 
regiments  were  constantly  receiving  recruits  from  France,  whence  it 


e  Historical  [en. 

may  be  inferred  that  the  disease  was  brought  by  carriers.  The  brunt 
of  the  epidemic  fell  upon  Naples  and  Calabria.  The  disease  was  present 
in  Sicily  in  1844.  Corfu  had  already  been  visited  by  the  disease  in 
1840,  the  infection  having  apparently  been  brought  from  the  port  of 
Sinigaglia  near  Ancona.  In  1844  an  epidemic  occurred  at  Gibraltar, 
where  the  usual  course  of  events  was  reversed,  the  civil  population 
being  the  ones  to  suffer,  while  the  garrison  went  largely  unscathed. 
The  strict  regulations  separating  the  military  and  civil  population, 
which  have  always  been  in  force  in  this  station,  probably  account  for 
the  escape  of  the  soldiers.  In  the  spring  of  1845  epidemic  meningitis 
appeared  in  Denmark,  Copenhagen  in  particular  suffering.  In  the 
following  winter  it  reappeared,  Iceland  also  being  afEected.  The 
United  Kingdom  had  hitherto  escaped  the  visitation  of  the  disease, 
with  the  exception  of  two  small  epidemics  which  are  cited  by  Ormerod. 
The  first  occurred  in  a  Dartmoor  village  in  1807,  but  the  recorded 
description  by  Gervis  leaves  the  nature  of  the  disease  extremely  doubtful. 
The  second  occurred  at  Sunderland  in  1830 ;  its  description,  however, 
was  not  published  by  Scott  until  thirty-five  years  later;  so  that  the 
nature  of  the  outbreak  is  without  adequate  confirmation.  In  the 
winter  of  1845-6  the  disease  first  appeared  in  an  epidemic  form  in  the 
workhouses  at  Dublin,  Bray  and  Belfast.  A  few  cases  occurred  also 
in  Liverpool,  and  a  small  epidemic,  as  to  whose  nature  some  doubt 
exists,  is  recorded  by  Brown  at  Eochester  in  1850.  One  case  occurred 
at  Haslar  Hospital.  In  America  a  second  visitation  of  epidemic 
meningitis  occurred  in  1841.  The  disease  first  appeared  in  Tennessee 
and  Alabama.  In  1845  and  the  following  years  outbreaks  occurred  in 
Illinois,  Arkansas,  Missouri  and  New  Orleans.  In  1848  it  spread  east- 
wards to  Pennsylvania,  and  appeared  in  Massachusetts,  but  was  limited 
to  two  small  townships.  A  somewhat  striking  feature  in  this  second 
visitation  is  the  immunity  enjoyed  by  the  New  England  states,  which 
suffered  so  severely  in  the  first  epidemic.  It  may  be  remarked,  however, 
that  the  shifting  character  of  the  population  in  the  States  of  the  Middle 
West  at  this  date  may  have  had  some  influence  on  the  propagation  of 
the  epidemic. 

Hirsch's  third  period  begins  with  the  year  1854,  when  the  disease 
appeared  for  the  first  time  in  Sweden.  The  method  of  spread  of  this 
epidemic  differed  in  a  marked  manner  from  that  observed  in  previous  ones. 
In  place  of  widely  scattered  isolated  centres,  the  disease  advanced  in 
a  systematic  manner  from  the  south-west  in  a  northerly  direction. 
With  each  succeeding  annual  recrudescence,  fresh  outbreaks  occurred 


i]  Historical  7 

near  the  northern  limit  of  the  previous  manifestation.  The  localities 
stricken  by  the  epidemic  of  the  year  before  escaped,  while  with  each 
recurrence  of  the  disease  fresh  districts  were  invaded.  The  disease  also 
spread  to  a  limited  extent  to  Norway.  In  Germany  a  few  small  and 
unimportant  epidemics  had  occurred  in  the  earlier  periods,  in  1827  in 
Rhenish  Prussia  and  in  1843  and  1851  at  Leipzig.  In  the  year  1863 
the  first  serious  outbreak  took  place  in  Silesia.  In  the  following 
year  East  and  West  Prussia,  Posen  and  Brandenburg  were  attacked. 
A  year  later  Hanover  and  Brunswick  were  in  turn  invaded.  In 
Southern  Germany  the  epidemic  first  broke  out  at  Nuremberg,  and 
appeared  coincidently  at  other  points  until  the  greater  part  of  Bavaria 
was  attacked.  Austria-Hungary  seems  to  have  been  largely  spared, 
with  the  exception  of  an  outbreak  in  an  orphanage  at  Vienna  and  small 
epidemics  at  Pola  and  Trieste.  In  Russia  there  were  minor  epidemics 
in  Moscow  and  Warsaw,  and  a  general  epidemic  in  the  Crimea.  In 
Greece  the  disease  first  appeared  in  1863-4  and  was  generally  epidemic 
in  1868-9.  Ireland  was  visited  for  the  second  time  in  1866-7,  an 
epidemic  occurring  in  Dublin  which  afEected  both  the  troops  and  the 
civil  population.  The  severity  of  this  epidemic  may  be  gauged  by  the 
frequency  of  haemorrhagic  rashes,  and  the  coincident  high  mortaUty. 
The  disease  also  appeared  at  Bardney  in  Lincolnshire  in  1867.  In 
connection  with  this  apparently  isolated  outbreak,  it  must  be  remembered 
that  farmers  near  the  recently  reclaimed  fenland  were  in  the  habit  of 
employing  gangs  of  reapers  from  Ireland,  and  that  this  may  have  been 
the  method  by  which  the  infection  was  imported.  In  this  epidemic 
wave,  which  was  both  more  concentrated  in  point  of  time  and  more 
universal  in  distribution  than  any  of  the  preceding  outbreaks,  America 
did  not  escape.  The  main  site  of  the  epidemic  was  not,  as  on  its  first 
appearance,  in  the  New  England  States,  nor,  as  in  the  second,  in  those 
of  what  is  now  styled  the  Middle  West,  but  mainly  in  the  Southern 
States.  Two  outbreaks  anticipated  the  European  epidemic,  one  in 
North  Carolina,  the  other  in  the  State  of  New  York.  The  Civil  War 
brought  in  its  train  all  the  attendant  circumstances  necessary  to 
engender  an  epidemic — overcrowding  of  troops  and,  with  their  move- 
ments, a  rapid  shifting  of  the  population.  The  disease  broke  out  in 
the  army  of  the  Potomac  during  the  winter  of  1861-2,  and  was  followed 
by  a  severe  epidemic  which  ultimately  involved  the  greater  part  of 
Pennsylvania;  Indiana  and  Virginia  were  next  attacked  in  1866-7, 
and  Kentucky  also  suffered.  Finally,  in  1873  the  disease  appeared  in 
Massachusetts,  and  at  Boston  in  1874.     The  American  epidemic  began 


8  Historical  [ch. 

earlier  and  lingered  longer  than  the  corresponding  wave  in  Europe, 
which  may  be  regarded  as  ending  in  1869.  After  this  date  the  appear- 
ance of  the  disease  was  for  many  years  limited  to  slight  and  widely 
separated  outbreaks. 

Hirsch's  fourth  period  begins  in  1876,  in  which  year  there  was  a 
minor  epidemic  at  Birmingham,  nineteen  cases  being  treated  at  the 
Queen's  Hospital  and  several  others  occurring  outside.  In  1877  a  small 
but  relatively  fatal  epidemic  occurred  at  Cape  Town.  In  the  succeeding 
years  epidemics  occurred  in  Silesia,  Poland,  Galicia  and  Hungary.  There 
were  also  small  epidemics  in  France,  Sicily  and  Greece  in  the  early 
eighties.  In  1885-6  there  were  slight  epidemics  of  the  disease  in  Paris, 
Milan  and  Turin.  The  appearance  of  the  disease  in  Vienna  at  this  date  has 
an  historical  interest  in  that  it  led  to  the  isolation  of  the  meningococcus. 
In  1885  the  disease  appeared  in  the  Fijian  Islands.  In  1884  an  epidemic 
occurred  near  Kilmarnock:  of  seven  persons  attacked,  five  died.  In 
1887  a  series  of  cases  in  infants  occurred  in  the  north  of  London. 
These  cases,  which  occurred  in  children,  were  distinguished  cUnically  by 
marked  retractions  of  the  head,  and  pathologically  by  the  presence  of 
purulent  meningitis.  They  were  treated  in  University  College  Hospital, 
and  during  the  same  period  two  cases  of  purulent  meningitis  in  adults 
were  admitted  with  marked  head  retraction.  Several  other  such  cases 
occurred  in  the  north  of  London.  The  cases  at  University  College 
Hospital  were  observed  by  one  of  us,  and  were  regarded  by  the  late 
Sir  William  Gowers  as  probable  examples  of  cerebro-spinal  meningitis. 
Kegarded  in  the  light  of  subsequent  experience,  no  doubt  would  occur 
as  to  the  true  nature  of  these  cases.  The  outbreak  in  the  eighties 
would  appear  to  have  been  of  a  very  minor  character,  and  was  foUowed 
by  a  period  during  which  the  disease  remained  largely  quiescent. 

Before  the  appearance  of  the  next  epidemic  wave,  which  Osier 
regards  as  the  fifth,  the  whole  aspect  of  the  disease  as  regards  diagnosis 
had  been  entirely  changed,  by  the  isolation  of  the  causative  organism  on 
the  one  hand,  and  the  demonstration  of  the  facility  and  safety  of  the 
operation  of  lumbar  puncture  on  the  other.  From  this  time  statistics, 
whether  of  the  frequency  of  occurrence  of  the  disease,  or  of  its  distribu- 
tion, or  of  the  results  of  treatment,  acquire  a  new  and  more  accurate 
significance.  Another  discovery  was  made  in  1898,  which  has  also 
proved  to  be  of  great  importance  from  the  epidemiological  point  of 
view.  The  identification  of  the  meningococcus  as  the  cause  of  posterior 
basic  meningitis  by  Still  put  an  entirely  new  aspect  on  the  relation 
of    one   epidemic  to   another.      Posterior  basic  meningitis  was  first 


i]  Historical  9 

differentiated  clinically  as  a  form  distinct  from  other  varieties  of  meningitis 
by  Gee  and  Barlow  in  1878,  but  its  relationship  to  epidemic  meningitis 
was  not  then  realized.  Since  its  identification,  posterior  basic  meningitis 
has  been  recognized  every  year  in  most  of  the  large  towns  of  England, 
and  is  to  be  looked  upon  as  a  sporadic  form  of  epidemic  meningitis 
which  is  always  present.  It  is  not  necessary,  therefore,  to  attempt  to 
trace  a  direct  spread  for  any  particidar  epidemic,  since  the  matter  is 
more  a  question  of  the  occurrence  of  the  appropriate  conditions  than 
of  the  introduction  of  an  extraneous  infective  agent.  In  the  year  1898 
there  was  a  recrudescence  of  cerebro-spinal  fever  in  France.  America 
again  suffered  a  visitation  in  this  year,  which  has  acquired  significance 
from  the  researches  then  conducted  by  Councilman,  Mallory  and  Wright. 
In  1901-3  a  severe  epidemic  occurred  in  Portugal  in  which  there  were 
no  less  than  3000  cases,  a  heavy  toll  in  proportion  to  the  population. 
This  epidemic  has  further  interest  in  that  lumbar  puncture  as  a  thera- 
peutic method  was  then  first  employed  by  Fran9a.  In  1904-5  a 
severe  epidemic  broke  out  in  New  York  and  the  New  England  States. 
In  New  York  alone  in  1905  the  cases  amoimted  to  2755.  This  epidemic 
lasted  with  diminishing  iatensity  through  1906  and  1907 ;  its  close  is 
remarkable  in  that  serum  treatment  was  then  first  introduced  by 
Flexner.  Silesia  was  once  more  attacked,  3317  cases  occurring  there 
during  the  year  1907.  In  the  year  1911  an  outbreak  occurred  in  the 
South-Western  States  of  America.  The  succeeding  year  1912  witnessed 
an  extensive  epidemic  in  the  State  of  Texas,  the  disease  originating  in 
the  larger  towns,  notably  Dallas,  and  thence  spreading  to  the  country 
districts.  In  this  epidemic  Sophian  had  great  opportunities  of  studying 
the  clinical  and  bacteriological  features  of  the  disease  and  utilized 
them  admirably. 

In  the  four  preceding  periods  of  Hirsch's  classification  the  United 
Kingdom  had  enjoyed  a  marked  relative  immunity.  The  Irish 
epidemics,  and  a  comparatively  unimportant  one  at  Birmingham  in  the 
seventies,  constitute  the  only  outbreaks  to  which  the  term  epidemic  can 
fitly  be  applied.  It  was  not  until  the  earlier  years  of  this  century 
that  extensive  epidemics  of  the  disease  have  occurred  within  these 
islands.  In  1902  a  small  epidemic  of  forty  or  fifty  cases  occurred  in 
Dublin,  but  no  extension  followed.  In  the  end  of  the  year  1906  cases 
began  to  appear  in  Belfast,  a  month  later  five  members  of  one  family 
were  attacked  within  thirty  hours  of  each  other.  The  epidemic  how- 
ever did  not  begin  in  earnest  until  the  end  of  February  1907.  By  the 
end  of  August,  Eobb  had  treated  275  cases  in  the  Belfast  hospitals. 


10  Historical  [ch. 

During  the  next  year  ninety  cases  passed  through  the  Belfast  fever 
hospitals.  Up  to  the  end  of  1914  only  twenty-seven  additional  cases 
had  come  under  Robb's  care.  From  this  it  would  appear  that  the 
epidemic  was  at  its  maximum  in  the  first  year,  and  had  practically 
disappeared  at  the  end  of  eighteen  months.  The  total  epidemic  in 
1907-8  consisted  of  725  cases,  about  half  of  which  therefore  passed 
through  Robb's  hands.  Almost  simultaneously  with  the  outbreak  in 
Belfast  cases  began  to  appear  in  Glasgow.  Currie  and  MacGregor  state 
that  the  first  cases  were  admitted  into  the  Glasgow  Fever  Hospital  in 
May  1906.  For  the  rest  of  the  year  cases  averaged  about  seven  per 
month,  but  early  in  1907  the  disease  became  epidemic,  and  in  April 
of  that  year  forty-two  cases  were  admitted.  In  the  two  years  1906-7 
and  1907-8,  330  cases  were  admitted  into  the  Belvedere  Fever  Hospital. 
The  total  number  of  cases  in  Glasgow  was  1238 ;  according  to  Chalmers 
more  than  a  thousand  of  these  occurred  in  the  period  1906-7.  This 
epidemic  thus  presents  a  marked  similarity  to  that  in  Belfast  as  regards 
the  abrupt  decline  noticeable  in  the  second  year.  Edinburgh  was  also 
attacked  during  the  same  period  but  to  a  lesserdegree,  138  cases  occurring. 
During  and  after  this  main  outbreak  a  few  small  and  scattered  epidemics 
have  occurred  up  and  down  the  country.  The  continuance  of  the 
disease  led  the  authorities  to  make  it  notifiable  in  1912.  In  the  years 
1912,  1913,  1914  about  300  cases  were  notified  annually. 

The  early  months  of  the  year  1915  witnessed  an  epidemic,  the  first 
of  its  kind  really  to  affect  England  as  a  whole ;  previous  epidemics  had 
been  confined  to  the  industrial  towns  of  Scotland  and  Ireland.  But 
conditions  had  entirely  changed,  the  whole  face  of  the  country  was 
covered  by  soldiers  in  training,  by  force  of  circumstances  overcrowded 
in  billets  and  exposed  to  changes  of  weather  without  any  adequate 
means  of  drying  themselves.  Conditions  such  as  these  tended  to  a 
lowering  of  individual  resistance,  the  changes  being  greater  than  would 
ever  occur  in  any  community  of  men  during  peace  time.  Owing  to 
the  system  of  billeting,  soldiers  and  civilians  were  brought  into  close 
contact,  consequently  the  disease  was  almost  equally  distributed  amongst 
the  military  and  civil  population.  The  main  distribution  was  in  places 
where  troops  were  most  closely  concentrated,  namely  on  Salisbury  Plain, 
at  Aldershot,  in  the  London  area  and  the  Eastern  Counties  of  England. 
The  statistics  of  the  epidemic  of  1914-15  are  still  in  a  condition  too 
incomplete  for  any  final  study.  Col.  Reece  has  however  published  full 
statistics  of  the  cases  which  occurred  amongst  the  troops. 

In  the  years  1906-7-8  extensive  outbreaks  occurred  in  West  Africa 


i]  Historical  11 

and  the  Northern  Territories  of  the  Gold  Coast;  that  of  1907  is  stated 
to  have  caused  no  less  than  10,000  deaths.  East  Africa  was  visited 
by  an  epidemic  in  1913,  which  is  of  interest  as  treatment  by  soamin 
was  attempted  for  the  first  time  to  any  extent.  An  outbreak  amounting 
to  some  200  cases  occurred  in  the  Transvaal  in  1907.  Col.  Wilkinson 
states  that  outbreaks  of  the  disease  occur  from  time  to  time  in  India, 
notably  in  jails  and  famine  rehef  camps.  Here  again  the  conditions 
hitherto  noted  in  connection  with  the  spread  of  the  disease,  over- 
crowding of  a  shifting  population,  are  a  marked  feature.  The  foregoing 
facts  prove  that  the  disease  is  more  widespread  in  tropical  countries 
than  is  generally  recognized.  A  survey  of  its  geographical  distribution 
shews  that  epidemics  have  occurred  from  the  Equator  to  within  the 
Arctic  circle.  Nor  has  the  disease  been  confined  to  one  hemisphere 
alone,  the  southern  hemisphere  has  been  afEected  as  well  as  the 
northern.  Chmate  fer  se  can  thus  have  but  sUght  influence  on  the 
occurrence  of  an  outbreak,  an  explanation  must  rather  be  sought  in 
the  hygienic  conditions  of  any  given  community. 

Regarded  from  the  standpoint  of  our  present  knowledge  of  the 
disease,  a  survey  of  the  epidemics  of  the  past  reveals  several  striking 
characteristics.  The  importance  of  the  carrier  in  spreading  the  disease 
is  illustrated  again  and  again  in  different  epidemics.  The  most  remark- 
able illustration  is  the  almost  fantastic  story  of  the  wanderings  of  the 
18th  Light  Infantry,  who  during  the  course  of  a  few  years  carried  the 
disease  from  one  end  of  France  to  the  other.  The  outbreak  in  Southern 
Italy,  which  began  in  1839,  was  almost  certainly  due  to  the  presence  of 
a  French  garrison  at  Ancona,  the  starting-place  of  the  outbreak. 
Recruits  were  constantly  arriving  in  this  garrison  from  France,  where 
the  disease  had  been  prevalent  for  some  years.  The  frequency  with 
which  seaports  have  been  either  the  starting-place  of  an  epidemic  or 
its  exclusive  seat,  indicates  again  the  part  played  by  carriers  from 
overseas  in  infecting  the  population.  The  infection  of  the  island  of 
Corfu  from  the  port  of  Sinigaglia  is  an  instance  in  point,  and  it  may  be 
surmised  that  the  Albenga  epidemic  had  a  similar  origin.  Outbreaks 
of  any  magnitude  in  the  British  Isles  previous  to  1914  had  always 
occurred  in  seaports.  It  is  probable  thut  the  importation  of  a  carrier 
does  not  lead  to  an  immediate  epidemic,  as  is  instanced  by  the 
outbreak  in  the  Landes,  when  an  interval  of  three  to  four  years 
elapsed  between  the  first  case  and  a  general  prevalence  of  the  disease. 
The  frequent  occurrence  of  outbreaks  in  camps,  garrisons  and  seaports 
is  also  partially  accounted  for  by  the  inevitable  occurrence  of  periods 


12  Historical  [ch.  i 

of  temporary  overcrowding  connected  with  the  life  of  such  places.  By 
contrast  it  may  be  noted  that  the  occurrence  of  a  case  on  board  ship 
is  a  very  rare  event.  In  the  epidemic  of  1914-15,  in  the  Royal  Navy 
out  of  a  total  of  170  cases  only  two  occurred  on  board  ship.  It  may 
be  inferred  that,  though  the  number  of  persons  crowded  into  a  ship  is 
considerable,  the  free  ventilation  renders  a  carrier  innocuous.  A  further 
condition  has  been  present  in  many  outbreaks.  Either  owing  to  war 
or  to  other  conditions,  the  population  in  the  site  of  the  outbreak  has 
been  constantly  shifting.  A  great  number  of  persons  are  thus  brought 
into  contact  with  each  other,  and,  as  the  influx  is  usually  greater  than 
the  housing  accommodation  can  deal  with,  this  contact  is  often  extremely 
intimate.  In  consequence  a  greater  number  of  persons  are  exposed  to 
carriers  under  conditions  favourable  to  the  spread  of  the  disease. 


CHAPTER   II 

SYMPTOMS 

Onset,  headache,  vomiting,  delirium,  stupor,  coma,  temperature,  pulse, 
respiration,  rashes,  herpes.  Aspect,  sphincters,  head  retraction,  other 
rigidities,  Kernig''s  sign,  reflexes,  ocular  palsies,  other  palsies, 
nervous  sequelae.  Affections  of  the  eye,  optic  neuritis,  affections  of 
the  ear,  deafness.  Initial  Coryza,  the  throat,  the  lungs,  bronchitis, 
pneumonia,  affections  of  the  heart,  affections  of  the  kidneys. 

In  any  study  of  the  symptoms  of  cerebro-spinal  fever  the  subject 
has  to  be  approached  from  two  points  of  view;  the  coiixse  of  an  acute 
specific  fever  on  the  one  hand,  and  the  gradual  development  of  nervous 
phenomena,  due  to  changes  in  the  organ  on  which  the  brunt  of  the 
infection  falls,  on  the  other.  As  a  general  rule,  cerebral  or  spinal 
symptoms  develop  some  time  after  the  patient  has  been  stricken  down 
by  an  ob^aously  acute  illness.  The  onset  of  cerebro-spinal  fever  is  as 
a  rule  sudden.  Like  pneumonia  and  typhus,  the  disease  is  frequently 
ushered  in  by  a  rigor.  In  the  greater  number  of  our  cases,  the  patient 
was  apparently  in  his  ordinary  health  when  he  suddenly  began  to  shiver, 
this  varying  from  a  mere  sensation  of  chilhness  to  a  prolonged  period 
of  violent  shaking.  In  other  cases  again  the  onset  is  more  insidious, 
a  short  period  of  general  malaise  with  some  headache  being  succeeded 
by  an  increase  of  headache,  until  the  supervention  of  vomiting  finally 
calls  attention  to  the  probable  nature  of  the  malady.  A  striking 
feature  in  many  cases  is  complete  loss  of  appetite,  amounting  even  to 
absolute  revulsion  against  any  kind  of  food.  The  onset  in  the 
fulminating  or  foudroyant  type  is  very  sudden,  coma  may  occur  either 
during  sleep,  or  an  hour  or  two  after  onset.  One  of  our  cases,  which 
terminated  fatally,  was  found  unconscious  in  the  morning,  having  been 
in  ordinary  health  the  night  before.  Another  case  was  found  dead  in 
bed.  That  an  onset  of  such  startling  suddenness,  though  usually  asso- 
ciated with  a  fatal  result  is  not  necessarily  so,  the  following  case  will 
shew.  An  officer's  servant,  who  had  been  at  his  work  the  night  before, 
was  found  unconscious  in  bed  at  2  a.m.,  and  removed  to   the  base 


14  Symptoms  [CH. 

hospital  at  Cambridge.  On  admission  he  was  unable  to  swallow,  there 
was  retention  of  urine  and  nystagmus ;  lumbar  puncture  was  performed 
and  repeated  daily  for  three  days.  At  the  end  of  24  hours  he  was  able 
to  swallow,  and  was  entirely  free  from  all  symptoms  on  the  sixth  day. 
This  patient  remembered  nothing  from  going  to  bed  before  the  attack 
imtil  the  fifth  day.  From  this  it  would  appear  that  the  onset  may  be  so 
sudden  as  to  overwhelm  the  sensorium  without  any  warning  symptom, 
and  yet  be  followed  by  a  rapid  recovery.  The  immediate  and  salutary 
effect  of  lumbar  puncture  would  suggest  the  view  that  the  symptoms 
were  largely  due  to  sudden  rise  of  intracranial  pressure.  In  another 
case  the  patient  was  suddenly  seized  with  dizziness  while  riding  on  a 
bicycle;  he  fell  from  his  machine  and  with  difficulty  made  his  way  for 
a  mile  to  his  home;  his  temperature  was  then  found  to  be  104.  Delirium 
rapidly  set  in,  but  after  a  tedious  illness  eventually  he  completely 
recovered.  The  disease  may  begin  during  convalescence  from  influenza, 
measles  or  pharyngitis,  and  thus  closely  simulate  a  relapse.  The 
preliminary  rigor  of  the  onset  is  either  accompanied  or  rapidly  followed 
by  headache;  this  varies  in  its  initial  severity  and  the  rapidity  with 
which  it  becomes  more  intense.  The  headache  generally  affects  the 
whole  head,  occasionally  it  is  more  marked  in  the  occipital  region, 
occasionally  in  the  frontal.  In  none  of  otir  cases  was  it  ever  imilateral. 
When  once  the  headache  has  begun,  it  steadily  increases  in  intensity, 
intermissions  are  uncommon  and  the  pain  is  rarely  soothed  by  drugs. 
When  persisting,  the  pain  may  be  of  the  most  agonizing  description,  the 
patient's  fortitude  completely  breaking  down,  till  he  fills  the  ward  with 
his  cries  and  moans.  The  headache  continues  for  days,  even  when  a 
state  of  delirium  is  present,  but  may  at  any  time  be  replaced  by  coma. 
Accompanying  the  headache  there  is  a  varying  degree  of  photophobia; 
but  this  is  not  nearly  so  marked  an  early  symptom  as  in  tubercular  menin- 
gitis. With  the  onset  of  headache,  vomiting  occurs  in  practically  all 
cases  within  a  comparatively  short  space  of  time.  The  period  of  its 
first  appearance  varies  from  about  three  hours  to  three  days ;  it  may  be 
entirely  absent  in  the  fulminating  type.  In  one  fatal  case  there  was 
no  vomiting,  but  severe  diarrhoea.  The  urgency  of  vomiting  varies 
markedly  in  the  different  cases:  in  some  it  is  limited  to  one  or  two 
attacks,  in  others  it  is  continuous  for  24  hours.  On  the  whole,  it  may  be 
said  that,  although  always  present  to  some  extent,  it  is  not  so  continuous 
and  distressing  a  symptom  as  in  other  cerebral  affections. 

A  variable  time  after  headache  and  vomiting,  delirium  makes  its 
appearance.     This  symptom  is  a  fairly  common  one  in  adult  cases; 


n]  Symptoms  15 

out  of  thirty-six  consecutive  cases  delirium  occurred  in  twenty;  ten 
passed  gradually  into  a  state  of  coma  without  the  supervention  of 
delirium,  and  in  six  cases  delirium  was  not  noted  at  all.  The  date  of 
onset  of  the  dehrium  varies  within  considerable  limits,  the  earhest 
being  three  hours  from  first  feeling  ill,  and  the  latest  on  the  sixth  day. 
In  one  case  delirium,  which  was  absent  during  the  primary  attack, 
made  its  appearance  during  a  recrudescence.  In  the  majority  of  cases, 
this  symptom  was  first  observed  on  the  second  or  third  day.  The 
character  of  the  delirium  varies  from  mere  muttering  to  absolutely 
maniacal  excitement,  the  dehrium  ferox  of  older  writers.  Many  of  the 
patients  are  very  noisy,  one  man  in  his  waking  moments  shouted  so 
loud  as  to  be  heard  200  yards  from  the  hospital.  Another  case  was 
regarded  at  first  as  dehrium  tremens.  A  feature  of  the  delirium  is 
constant  reference  to  the  extreme  intensity  of  the  headache.  Headache 
does  not  cease  when  delirium  begins.  With  the  dehrium  there  is 
associated  a  considerable  degree  of  restlessness,  the  patient  constantly 
trying  to  get  out  of  bed ;  some  cases  may  be  so  violent  as  to  require  men 
to  hold  them.  Associated  with  the  general  restlessness  in  less  active  forms 
of  delirium,  there  is  sometimes  seen  the  symptom  called  by  the  old 
physicians  floccillation  or  carphology :  this  consists  in  constant  movement 
of  the  hands  over  the  bed-clothes  or  in  front  of  the  face,  the  purpose 
apparently  being  to  draw  some  object  towards  them.  It  does  not  occur 
with  any  marked  frequency,  and,  although  only  present  in  grave  cases, 
does  not  appear  to  have  the  sinister  significance  which  its  presence 
betokens  in  typhus.  This  carphology  must  be  distinguished  from  the 
fighting  movements  of  the  hands  such  as  are  seen  in  cases  of  extreme 
dyspnoea.  Subsultus  tendinum  occurs,  but  this  again  is  not  of  such 
grave  significance  as  in  other  diseases.  In  a  considerable  proportion 
of  cases  delirium  is  succeeded  by  stupor,  which  after  an  interval  of 
varying  length  passes  into  coma.  In  other  cases  again,  coma  may 
supervene  upon  the  stage  of  headache  and  vomiting  without  the 
preliminary  stage  of  delirium.  The  fulminating  case  may  pass  into 
a  state  of  coma  without  any  warning  symptoms.  Coma  was  present 
at  some  stage  or  another  in  twenty  out  of  thirty-sLs  of  our  cases.  The 
degree  of  stupor  or  coma  varies  markedly,  in  the  more  severe  types 
the  condition  is  profound.  The  patient  lies  like  a  log,  unable  to 
swallow,  mucus  rattUng  in  his  throat :  desperate  as  such  cases  appear, 
some  of  them  make  a  rapid  recovery,  if  the  pressure  is  reheved  early 
enough.  In  other  cases  there  is  a  period  of  semi-coma,  from  which  the 
patient  can  be  roused  to  take  nourishment  or  even  to  answer  questions. 


16 


Symptoms 


[CH. 


Possibly  in  no  disease  is  the  temperature  less  a  criterion  of  the 
severity  of  the  case  than  in  cerebro-spinal  fever.  As  a  rule,  in  mild  or 
sub-acute  cases,  the  temperature  rises  at  once  to  101-103  and  remains 
near  this  level  for  several  days,  with  considerable  daily  remissions. 
As  lumbar  puncture  exercises  a  considerable  influence  on  the  course  of 
the  temperature,  it  is  difficult  to  estimate  the  distinctive  temperature 
curve.  Following  the  initial  rise,  the  temperature  follows  no  regular 
course;  remissions  with  an  apyrexial  period  followed  by  a  subsequent 
further  rise  of  temperature  commonly  occur.  Lumbar  puncture  usually 
produces  a  definite  drop,  followed  by  a  rise  after  a  varying  interval. 
Chart  1  shews  the  temperature  curve  in  an  acute  case  in  which  lumbar 
puncture  was  repeatedly  performed.  The  height  of  the  temperature 
forms  no  criterion  of  the  severity  of  the  disease,  some  of  the  most 

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the  temperature  in  two  cases,  one  of  which  was  fatal  within  30  hours, 
the  other,  already  referred  to,  was  found  comatose  in  bed  but  re- 
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apyrexial  periods  followed  by  occasional  recrudescence  of  fever  which  is 
usually  attended  by  a  return  of  symptoms.  The  fever  in  some  cases 
presents  a  strange  resemblance  to  a  tertian  ague,  in  others  to  a 
quotidian.  Chart  4  is  an  example  of  this.  Just  before  death  the 
temperature  may  rise  suddenly  to  105  or  more,  more  usually  the 
previous  level  is  maintained  till  death.  Fulminating  cases  differ  in 
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temperature  to  below  97. 

In  the  earlier  stages  the  pulse  is  somewhat  quickened,  but  as  a  rule 


n] 


Symptoms 


17 


not  to  the  extent  wliicli  would  be  expected  from  the  temperature. 
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with  the  fluctuations  in  temperature.  The  occurrence  of  a  pulse  of 
60  to  80  accompanying  a  temperature  of  101-103  is  not  imcommon  in 
the  early  stages  of  the  disease,  and  is  of  considerable  diagnostic  import- 
ance.    Nine  out  of  twenty-three  cases  which  came  under  our  care  shortly 


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after  onset,  shewed  a  marked  slowness  of  the  pulse  with  high  temperature. 
At  a  later  period  the  pulse  changed  from  its  previous  slow  full  character, 
becoming  much  more  rapid.  In  sub-acute  cases  the  pulse  is  some- 
times irregular  at  quite  an  early  stage.  In  the  fulminating  and  acute 
varieties  the  pulse  is  very  quick  and  running  from  the  onset.  When 
F.  &  a.  2 


18  Syinptoms  [CH. 

hydrocephalus  supervenes,  the  pulse  may  suddenly  change  from  its 
former  character  and  become  extremely  rapid  and  feeble.    - 

The  respirations  in  the  majority  of  cases  are  slightly  but  not  markedly 
quickened;  in  some  however  the  respirations  are  very  rapid,  forty  to 
fifty  in  the  minute  without  any  pulmonary  compUcation.  They  may  vary 
from  time  to  time,  and  may  drop  at  once  to  normal  on  the  administration 
of  an  anaesthetic  before  lunibar  puncture  has  been  performed,  which 
proves  the  central  origin  of  the  condition.  With  this  rapid  respiration 
there  may  be  almost  rhythmical  variation  in  frequency  and  depth; 
and  not  uncommonly  sighing  respiration  is  noticeable.  This  type  of 
respiratory  irregularity  is  called  Biot's  respiration,  or  cerebral  breathing. 
Cheyne-Stokes  breathing  is  present  as  a  terminal  symptom  both  in  the 
acute  cases  and,  notably,  in  cases  which  are  in  a  condition  of  hydro- 
cephalus. In  the  fulminating  cases  urgent  dyspnoea  is  a  marked 
symptom.  The  breathing  is  very  rapid,  60  or  more  to  the  minute, 
while  the  patient  beats  the  air  with  his  hands.  Death  may  occur  from 
sudden  respiratory  failure,  the  heart  continuing  to  beat  for  some  time 
after  respiration  has  stopped.  This  method  of  death  is  more  frequently 
met  with  in  this  disease  than  in  others,  and  is  due  to  pressure  on  the 
fourth  ventricle.  The  pulse  respiration  ratio  is  of  some  diagnostic 
importance,  it  never  exhibits  the  regular  increased  ratio  seen  in  pneu- 
monia. 

The  aspect  of  the  patient  in  the  early  stage  is  characteristic,  the 
face  is  usually  flushed  and  the  expression  one  of  suffering,  which  later,  as 
stupor  approaches,  gives  place  to  a  heavy  dull  look  somewhat  resembhng 
typhus.  The  patient  usually  lies  curled  up  in  bed  during  the  earlj^ 
stage,  but,  as  retraction  becomes  marked,  assumes  the  unmistakable 
attitude  which  this  symptom  produces.  Sometimes  the  patient  rests 
on  his  elbows  face  downwards,  supporting  the  head  with  the  hands. 

Four  distinct  varieties  of  rash  may  be  observed  in  the  course  of  the 
disease. 

(1)  A  macular  rash  ^^ath  fairlj^  uniform  distribution ; 

(2)  A  fugitive  erythema  appearing  in  different  parts  of  the  body; 

(3)  A  petechial  rash; 

(4)  Vibices  or  large  purpuric  spots. 

The  macular  rash  (Plate  I)  follows  a  fairly  definite  course  both  in 
aspect,  distribution  and  date  of  eruption.  The  individual  maculae 
vary  in  size  from  a  millet  seed  to  a  No.  1  shot,  and  they  do  not  disappear 
on  pressure.  The  variations  in  colour  may  represent  any  hue  from  that 
of  a  scarlet  geranium  to  a  ripe  grape.     The  distribution  is  fairly  uniform, 


ii]  Symptoms  19 

the  rash  being  first  discernible  on  the  abdomen ;  it  subsequently  appears 
on  the  thighs,  the  extensor  surfaces  of  the  forearms  and  legs,  and  finally 
on  the  backs  of  the  hands  and  dorsum  of  the  foot.  The  maculae  as  they 
fade  leave  a  slate-blue  staining.  This  rash  occurred  in  ten  out  of  thirty- 
nine  of  our  cases,  and  appeared  in  the  majority  of  instances  on  the 
fourth  day.  In  one  case  it  was  reported  to  have  appeared  on  the 
second  day,  and  in  a  very  severe  case  it  only  appeared  on  the  eighth 
day,  when  convalescence  had  set  in,  but  had  been  preceded  by  patches 
of  fugitive  erythema.  This  rash  does  not  come  out  in  successive  crops, 
it  begins  to  fade  rapidly,  and  at  the  end  of  four  days  nothing  but  staining 
is  to  be  observed.  The  eruption  may  be  regarded  as  the  true  specific 
rash  of  the  fever,  though  it  is  probably  the  least  regular  of  all  the 
exanthemata. 

The  erythematous  rash  (Plate  II,  fig.  1)  is  analogous  to  the  transient 
erythema  which  may  precede  the  eruption  in  small-pox  or  typhus. 
The  erythema  may  appear  on  any  part  of  the  body  and  at  almost  any 
stage  of  the  disease.  The  rash  is  uniform  or  mottled,  and  varies  in 
colour  from  pink  to  bluish  red.  The  duration  is  usually  short,  lasting 
only  a  few  hours.  In  one  instance  sUght  staining  was  left  behind. 
This  rash  occurred  in  six  of  our  cases,  two  of  which  were  fatal.  The 
latest  date  on  which  it  made  its  appearance  was  the  thirteenth  day. 

The  third  form  of  skin  eruption  is  the  petechial  rash  (Plates  II,  fig.  2 
and  III).  This  consists  of  small  papules,  varying  in  size  from  a  pin's 
head  to  a  peppercorn,  of  a  purple  red,  or  bright  copper  colour.  In 
distribution  it  reveals  its  traumatic  character,  being  always  found  at 
points  where  pressure  is  most  unavoidable.  Consequently  it  makes 
its  appearance  on  the  knees,  elbows,  malleoli  and  the  points  of  the 
shoulders.  Where  the  patient  has  scratched  himself  or  been  bruised, 
patches  of  petechiae  with  surrounding  erythematous  redness  will  be 
found.  The  nature  of  the  eruption  is  evidence  of  profoimd  toxaemia, 
it  occiirred  in  six  cases  out  of  thirty-eight  and  was  in  each  instance 
accompanied  by  a  fatal  result.  It  appeared  from  the  first  to  the  third 
day. 

The  purpuric  rash  (Plate  IV)  is  merely  an  exaggerated  form  of  the 
last-mentioned.  It  occurs  in  large  spots,  "vibices"  of  the  older  writers, 
varying  in  size  from  that  of  a  bean  to  a  pea's  pod,  and  of  a  dark 
purple  colour.  The  distribution  is  irregular,  in  the  only  case  which  came 
imder  our  observation  it  occurred  on  the  thighs,  knees,  ankles,  dorsum 
of  foot  and  was  well-marked  on  the  face.  This- latter  is  an  unusual 
distribution  in  the  purpuric  rashes  associated  with  other  diseases.     This 

2—2 


20  Symptoms  [CH. 

eruption,  whicli  is  common  to  all  profound  infections  and  is  identical 
with  the  mediaeval  plague  spot,  only  occurs  in  fulminating  and  fatal 
cases. 

In  a  considerable  proportion  of  cases  herpes  appears ;  this  symptom 
occurred  in  fourteen  out  of  thirty-nine  of  our  cases.  The  eruption 
appears  from  the  third  to  the  sixth  day,  the  fourth  day  being  the  most 
usual.  In  one  fatal  case  the  vesicles  involved  the  entire  circumoral 
circle,  invading  the  mucous  membrane  to  a  considerable  degree.  Both 
facial  and  labial  herpes  co-existed  in  one  case,  while  in  another  the 
eruption  involved  the  ear  as  well  as  the  labial  and  submental  areas. 
Herpes  is  said  to  occur  on  other  parts  of  the  body,  but  this  did  not 
come  under  our  observation.  Netter,  however,  figures  an  eruption 
occurring  along  the  course  of  the  fifth  lumbar  nerve. 

The  above  train  of  symptoms  are  those  manifested  by  an  acute 
febrile  affection.  The  signs  connected  essentially  with  the  nervous 
system  may  now  be  considered.  The  sphincters  are  affected  in  a  large 
proportion  of  cases.  In  the  pubhshed  works  on  the  subject  no  great- 
stress  has  been  laid  on  this  symptom,  and  yet  it  is  of  considerable 
importance  from  the  point  of  view  of  early  diagnosis.  Out  of  thirty-nine 
of  our  cases,  the  sphincters  were  affected  at  one  time  or  another  in 
twenty-six.  Retention  of  urine  occurs  at  quite  an  early  stage  in  a  con- 
siderable number  of  cases,  in  one  this  was  the  sole  cause  of  the  man 
reporting  sick.  In  twenty  cases  a  catheter  had  to  be  passed  on  ad- 
mission, fourteen  of  these  cases  were  dehrious,  but  the  other  six 
were  quite  conscious,  and  in  no  sense  acutely  ill.  In  such  cases  the 
presence  of  retention  is  a  valuable  aid  to  early  diagnosis.  In  one  case 
there  was  difficulty  in  micturition,  but  no  retention.  Two  other  cases 
were  admitted  with  incontinence.  In  the  milder  cases  the  retention 
passed  off  after  the  first  or  second  lumbar  puncture ;  in  the  more 
severe  cases  which  recovered,  it  disappeared  after  two  or  three  days. 
Other  cases  developed  incontinence  both  of  urine  and  faeces  at  a  later 
date,  notably  those  which  became  hydrocephalic. 

Inability  to  swallow  was  present  in  six  cases  on  admission ;  they  were 
at  the  same  time  profoundly  unconscious.  Of  these,  three  died  and 
three  recovered.  One  fatal  case  became  unable  to  swallow  shortly 
after  admission.  In  all  our  other  cases,  the  power  of  swallowing  was 
never  entirely  lost,  though  great  difiiculty  was  met  with  in  getting 
them  to  take  food  by  the  mouth. 

In  association  with  the  headache  at  the  onset  of  the  disease,  there 
is  often  marked  pain  in  the  back  and  thighs  with  considerable  muscular 


n]  Symptoms  21 

rigidity.     Sooner  or  later  pain  and  rigidity  in  the  muscles  of  the  neck 
makes  its  appearance,  giving  rise  to  the  characteristic  sign  of  head 
retraction.     This  sign,  which  is  of  great  diagnostic  importance,  varies 
markedly  in  degree  and  in  the  date  of  its  appearance.     In  a  suspected 
case  the  muscles  of  the  neck  should  be  thoroughly  examined;  often 
nothing  but  some  shght  tenderness  can  be  made  out,  though  with  further 
manipulation  a  shght  amount  of  stiffness  can  be  ehcited.     This  stiffness 
differs  from  that  accompanying  rheumatic  affections,  in  that  the  latter 
is   lessened  by  manipulation,  whereas  the  former   is   increased.     The 
patient    is    imable    to    nod    the    head,    and   lies    on   his    side   rather 
than    on    his    back,    so    as    to    relax    the    muscles.      The    primary 
pain    and    stiffness    go   on   increasing   at   a   variable   rate,    until   the 
increasing  spasm  of  the  muscles  draws  the  head  back,  sometimes  even 
to  a  right  angle  to  the  trunk,  so  that  it  may  appear  to  rest  between  the 
shoiilders.     In  the  acute  cases  the  retraction  persists  without  variation 
for  some  days.     As  improvement  sets  in,  the  spasm  is  intermittently 
relaxed,  and  as  the  patient  approaches  convalescence,  remarkable  varia- 
tions are  observable  from  day  to  day.     In  milder  cases,  these  variations 
are  observable  from  the   beginning.     The   accompanying   illustration 
(Plate  V,  fig.  2)  shews  the  very  characteristic  appearance :     it  was  taken 
from  above  on  the  third  day  from  the  onset;    the  case  made  a  rapid 
recovery.     The  period  of   the   disease  when  this  sign  first  becomes 
obvious  is  subject  to  considerable  variations,  the  second  or  third  day 
being  the  commonest;   it  may,  however,  be  delayed  until  the  fifth  or 
sixth.     In  fulminating  cases  retraction  may  be  entirely  absent.     With 
this  exception,  however,  its  imiversal  presence  makes  its  appearance  of 
considerable  importance  from  a  diagnostic  point  of  view.     Its  presence 
is   always  indicative   of  the  existence   of  meningitis,  but,  owng  to 
its  occasionally  late  appearance,  its  absence  ought  not  to  be  given 
undue  weight  in  the  consideration  of  the  diagnosis,  and  should  not 
negative   an   immediate   lumbar   pimcture.     Head   retraction,    in   our 
experience,  is  to  some  extent  dependent  upon  increased  intracranial 
pressure;    it  was  often  greatly  diminished  or  entirely  reheved  by  the 
evacuation  of  a  considerable  quantity  of  cerebro-spinal  fluid  and  the 
reduction  of  the  pressure  to  the  normal.     This  immediate  rehef  shews 
that  it  is  not  muscular  in  origin,  but  is  dependent  on  irritation  of  the 
nervous  elements  provoked,  partially  at  all  events,  by  increased  intra- 
cranial pressure.     Following  head  retraction  this  rigidity  may  spread 
to  other  muscles  than  those  of  the  neck.     In  a  large  number  of  cases, 
the  condition  spreads  to  a  greater  or  less  degree  to  the  extensors  of  the 


22  Symptoms  [ch. 

spine.  Rigidity  of  the  lumbar  muscles  may  often  be  noticed,  and  in 
some  cases  this  may  produce  actual  opisthotonos.  Rigidity  of  the 
muscles  of  the  arms  and  legs,  notably  the  latter,  may  often  be  observed 
in  a  minor  degree.  Tonic  spasm  of  the  abdominal  muscles  may  be 
noticeable,  giving  rise  to  a  carinated  or  boat-shaped  appearance  of  the 
abdomen.  Rigidity  of  the  facial  muscles  may  be  observed,  which  in 
a  few  rare  instances  reaches  the  degree  of  actual  trismus. 

One  particular  form  of  rigidity  has  come  into  prominence  under  the 
name  of  Kernig's  sign  (Plate  VI,  fig.  1).  Kernig  of  Petrograd  first 
called  attention  to  this  phenomenon  in  1884.  The  sign  is  ehcited  in 
the  following  manner.  While  the  patient  is  lying  on  his  back  the 
thigh  is  flexed  at  a  right  angle  to  the  trunk.  This  brings  the  leg  at 
a  right  angle  to  the  thigh  at  the  knee ;  the  thigh  is  now  maintained 
in  the  same  position  by  placing  one  hand  on  the  patella,  while  an 
attempt  is  made  to  extend  the  leg  upon  the  thigh  with  the  other 
hand.  When  the  sign  is  present,  the  spasm  of  the  hamstring  muscles 
prevents  this  extension.  In  a  well-marked  case,  extension  cannot  be 
made  beyond  a  right  angle  with  the  thigh.  If  any  force  be  used, 
the  patient  at  once  complains  of  severe  pain  in  the  back.  Two  other 
methods  of  obtaining  the  sign  are  sometimes  practised : 

(a)  The  whole  leg  being  extended,  the  foot  is  raised  into  the  air. 
As  flexion  of  the  thigh  increases,  it  is  found  impossible  to  maintain 
the  extension  of  the  leg. 

(6)  The  patient's  shoulders  are  raised  from  the  bed.  As  the  trunk 
approaches  a  right  angle  with  the  thighs  the  knees  begin  to  flex. 

The  most  probable  explanation  of  the  sign  is  that  traction  on  the 
inflamed  lumbar  nerve  roots  causes  a  protective  spasm  in  the  muscles. 
The  accompanying  illustration  (Plate  VI,  fig.  1)  shews  clearly  the 
characteristic  contraction  of  the  hamstring  muscles.  The  appearance 
in  a  normal  person  is  illustrated  in  Plate  VI,  fig.  2. 

The  chnical  value  of  the  sign  cannot  be  exaggerated.  In  cases  of 
influenza  and  other  febrile  conditions,  stiffness  may  prevent  complete 
extension,  but  this  in  such  a  minor  degree  as  to  be  readily  distinguished 
from  the  true  Kernig's  sign.  In  cases  of  sciatica  and  lumbago  extension 
cannot,  of  course,  be  obtained.  The  sign  is  also  normal  in  infants  up 
to  two  years  of  age.  With  these  reservations,  however,  the  sign  is  of 
the  greatest  value ;  it  occurs  in  all  but  fulminant  cases,  and  is  one  of  the 
earliest  symptoms  to  appear.  In  our  experience,  it  was  slightly  marked 
at  the  end  of  18  hours,  and  fully  developed  at  the  end  of  24.  Consider- 
able inequaUty  in  the  angle  of  extension  may  sometimes  be  observed 


nj  Symptoms  23 

between  the  two  sides,  presumably  o'wing  to  more  intense  meningeal 
inflammation  round  the  nerve  roots  of  the  one  side.  This  sign  is 
common  to  all  forms  of  spinal  meningitis  from  whatever  cause,  but  it 
is  a  most  valuable  indication  for  the  operation  of  lumbar  pimcture. 
The  other  reflexes  shew  no  particular  change.  The  knee  jerks  may  be 
absent  during  the  more  acute  stage,  and  return  with  convalescence; 
as  a  rule  they  are  present  and  may  be  exaggerated.  There  is  said 
occasionally  to  be  an  extensor  response  in  Babinski's  plantar  reflex,  in 
the  vast  majority  of  cases  the  response  is  flexor.  Ankle  clonus  has  not 
been  observed  by  us.  The  superficial  reflexes  are  preserved,  except  in 
profoundly  comatose  cases.  Some  observers  claim  that  the  abdominal 
reflexes  are  not  infrequently  absent. 

Paresis  or  palsy  of  particular  muscles  is  observed  in  a  small  pro- 
portion of  cases.  Of  afl'ections  of  the  ocidar  muscles,  strabismus  is 
occasionally  observed,  the  sixth  nerve  being  the  one  most  commonly 
affected.  Nystagmus  is  somewhat  more  common,  occurring  in  three 
out  of  thirty-nine  cases  in  our  experience.  Diplopia  occurred  in  about 
the  same  proportion  of  cases.  The  facial  nerve  is  sometimes  involved, 
though  the  affection  is  of  a  transitory  character.  The  hypoglossal 
nerve  may  be  afiected,  but  this  again  passes  off  in  a  short  time.  In 
one  case  under  our  care  there  was  internal  strabismus,  facial  palsy  and 
deviation  of  the  tongue,  all  of  which  passed  off  in  a  month.  In  this 
connection  it  is  of  interest  to  note  the  comparative  rarity  of  ocular 
palsy  compared  with  its  frequency  in  tubercular  meningitis,  a  valuable 
diagnostic  point.  These  palsies  disappear  entirely  as  convalescence  is 
estabhshed.  Hemiplegia  occurs,  though  rarely,  both  in  the  acute  and 
chronic  cases.  We  have  found  it  associated  wth  a  massive  deposit  of  pus 
over  the  Rolandic  area  (Plate  VII).  A  transient  monoplegia,  either  of  an 
arm  or  leg,  is  an  occasional  symptom,  it  usually  passes  off  as  recovery 
progresses.  Flaccid  paralysis  of  an  arm  or  leg  has  been  described  by 
Horder;  there  is  hyper-aesthesia  or  actual  pain  in  the  affected  hmb 
with  loss  of  tendon  reflexes,  wasting  and  reaction  of  degeneration. 
Recovery  is  usually  complete.  Some  convalescent  cases  are  very 
imsteady  on  their  legs  when  first  beginning  to  walk.  This  condition, 
according  to  Horder,  may  be  associated  with  exaggerated  knee  jerks, 
ankle  clonus  and  extensor  response.  Complete  recovery  usually  takes 
place.  Such  symptoms  were  not  observed  in  our  own  convalescent 
cases.  We  have,  however,  examined  two  cases  at  the  Hitchin  Con- 
valescent Home  which  somewhat  closeh^  simulated  Disseminated 
Sclerosis;     the   knee   jerks    were    exaggerated,    there   were    volitional 


24  Symptoms  [ch. 

tremors,  weakness  of  the  bladder  and  pallor  of  the  optic  discs.  Dis- 
turbance of  sensory  nerves  is  marked  by  hyper-aesthesia  of  varying 
distribution  and  intensity.  Two  of  our  cases  had  marked  hyper-aesthesia 
of  the  spine,  which  persisted  well  into  convalescence.  Vasomotor 
changes  are  indicated  by  the  almost  universal  presence  of  the  tache 
cerebrale. 

In  addition  to  the  affections  of  the  ocular  muscles  which  have  been 
already  described,  the  eye  itself  suffers  in  a  small  proportion  of  cases. 
Conjunctivitis  is  not  uncommon,  in  some  cases  it  is  unilateral.  The 
affection,  as  a  rule,  is  of  a  mild  character,  though  it  may  pass  into 
a  purulent  ophthalmia.  The  meningococcus  can  be  recovered  from 
the  pus.  Keratitis  is  an  uncommon  complication.  Flexner  quotes 
Uhtoff,  who  found  it  occurred  three  times  in  one  hundred  and  ten  cases. 
Iritis  and  iridochoroiditis  may  occur,  but  are  rare  complications. 
Iridocyclitis  leading  to  suppurative  panophthalmitis  and  consequent 
destruction  of  the  eyeball  is  the  most  serious  complication  to  be  feared. 
In  the  records  of  ninety-one  cases  amongst  soldiers  during  the  recent 
epidemic  we  only  found  this  complication  occur  once.  Morax  in  the 
Parisian  epidemic  observed  iridocyclitis  in  3  to  6  per  cent.  The 
affection  would  appear  to  be  usually  unilateral.  The  condition  of  the 
pupils  is  somewhat  characteristic ;  they  are  usually  dilated  and  sluggish 
in  their  response  to  light.  In  very  acute  cases  pin  point  pupils  may 
be  observed.  Inequality  of  the  pupils  is  infrequent,  though  it  occurs 
in  a  small  proportion  of  cases.  As  a  diagnostic  point  it  is  of  little 
value.  Optic  Neuritis  is  curiously  uncommon  compared  with  its  relative 
frequency  in  other  forms  of  meningitis.  Observations  as  to  its  frequency 
differ  markedly.  Randolph  of  Lonaconing  in  Maryland  found  it  present 
six  times  in  forty  cases,  while  Travers  Smith  in  Dubhn  found  it  entirely 
absent  in  thirty-six  cases.  In  thirty  cases  examined  ophthalmoscopi- 
cally  by  Major  Cooke  and  ourselves  at  the  First  Eastern  Hospital, 
optic  neuritis  was  entirely  absent.  These  cases  were  examined  at  all 
stages  of  the  disease,  and  many  of  them  more  than  once.  In  one  case 
slight  blurring  of  the  disc  was  noted,  which  entirely  disappeared  in  a 
short  time.  Extra  fullness  of  the  veins  in  hydrocephalic  cases  was  also 
observed.  Optic  neuritis  is  presumably  very  infrequent  and  of  little 
value  as  an  aid  either  to  diagnosis  or  prognosis.  Primary  optic  atrophy 
is  said  to  occur,  but  it  is  a  definitely  rare  complication. 

Deafness  is  the  most  frequent  affection  of  the  special  senses  to  be 
observed.  The  internal  ear  is  most  commonly  involved,  and  the 
affection  is  generally  bilateral.     This  symptom  usually  appears  in  the 


ii]  Symptoms  25 

second  or  third  week  of  illness.  In  some  cases  the  deafness  entirely 
passes  off  as  convalescence  progresses.  In  others  again  it  remains 
permanent,  and  may,  at  quite  an  early  period,  give  rise  to  auditory 
vertigo.  Middle  ear  disease  is  extremely  rare  as  a  complication.  Two 
of  our  cases  had  otorrhoea  long  preceding  the  onset  of  cerebro-spinal 
fever.  In  one  case  there  was  deafness  of  the  left  ear,  accompanied 
with  sloughing  of  the  right  eye. 

The  older  writings  on  the  subject  are  permeated  with  the  idea  that 
permanent  impairment  of  the  mental  faculties  is  a  sequel  to  be  dreaded. 
Thus  Fagge  speaks  of  the  number  of  imbeciles  left  in  the  wake  of  an 
epidemic  in  the  Ehineland.  Recent  experience  runs  entirely  counter 
to  this  view.  During  the  stage  of  recovery  patients  may  be  morose,  or 
unduly  irritable,  but  those  traits  pass  away  as  convalescence  increases. 
Chronic  cases  are  apt  to  become  neurasthenic,  and  exhibit  all  the 
typical  neurasthenic's  power  of  concentration  on  self ;  but  with  returning 
strength  this  attitude  gives  place  to  a  normal  healthy  habit  of  mind. 
When  there  has  been  long  and  persistent  headache,  which  is  probably 
due  to  a  minor  degree  of  hydrocephalus,  there  is  apt  to  be  some  mental 
enfeeblement,  but  if  convalescence  is  once  permanently  estabhshed 
this  is  recovered  from.  Out  of  thirty-six  patients  sent  to  the  Hitchin 
Convalescent  Home,  which  represented  all  the  tedious  and  lengthy 
cases  drawn  from  the  home  forces,  we  only  found  one  case  of  mental 
change.  This  man  had  complete  loss  of  memory,  accompanied  by 
palsy  of  the  right  arm,  suggesting  a  cortical  lesion  rather  than  any 
general  cerebral  degeneration.  Very  great  improvement  has  since 
taken  place  both  with  regard  to  his  arm  and  his  mental  condition. 

Rapid  wasting  occurs  after  about  the  fourth  or  fifth  day  in  severe 
cases  with  such  frequency  as  to  constitute  a  characteristic  feature  of 
the  disease.  In  patients  who  continue  to  exhibit  shght  though  still 
persistent  symptoms,  rapid  wasting  becomes  a  striking  feature.  Hydro- 
cephahc  cases,  which  drag  on  for  five  or  six  weeks,  exhibit  an  extreme 
degree  of  marasmus,  and  yet  there  may  be  no  difficulty  in  their  taking 
nourishment,  and  no  diarrhoea  or  vomiting  to  interfere  with  nutrition. 
It  would  appear  probable  that  this  wasting  is  essentially  trophic  in  its 
nature.  As  symptoms  abate,  nutrition  improves  rapidly  and  lost  flesh 
is  soon  regained.  A  somewhat  striking  feature  of  the  malady  is  the 
complete  return  to  health  both  in  body  and  mind  which  is  usually 
observed  even  in  the  most  severe  cases. 

In  a  small  proportion  of  cases,  arthropathies  may  make  their 
appearance.     The  degree  varies  from  mere  pain  and  stiffness  to  acute 


26  Symptoms  [ch. 

or  even  suppurative  arthritis.  The  meningococcus  has  been  recovered 
from  the  synovial  effusion.  Where  suppuration  has  occurred,  there  is 
usually  a  secondary  infection.  One  joint  only,  as  a  rule,  is  involved, 
though  multiple  arthropathies  have  been  observed.  No  joint  seems  to 
be  more  markedly  prone  to  be  affected  than  another,  with  the  possible 
exception  of  the  shoulder.  A  feature  of  these  arthropathies  is  that, 
with  appropriate  treatment,  very  little  pain  or  stiffness  is  left  behind. 
It  must  be  borne  in  mind  that  transitory  arthritis  may  appear  as  a 
sequel  to  serum  administration. 

Some  observers  regard  nasopharyngeal  catarrh  as  one  of  the  earliest 
symptoms  of  the  disease.  Lundie,  Thomas,  Fleming  and  Maclagan,  as 
the  result  of  their  investigations  in  the  Aldershot  Command  during  the 
epidemic  of  1915,  regard  a  naso-pharyngeal  catarrh  as  the  first  stage  of 
the  disease.  Their  views  meet  with  little  confirmation  from  other 
observers.  Of  thirty- nine  cases  treated  at  the  First  Eastern  General 
Hospital,  two  only  gave  a  history  of  preceding  sore  throat.  In  the 
other  cases,  there  was  nothing  abnormal  about  the  throat  on  their 
admission.  Further,  the  throats  of  proved  carriers  shew  no  evidence 
of  increased  catarrh  other  than  can  be  accounted  for  by  the 
presence  of  adenoids,  a  by  no  means  uncommon  associated  condition. 
A  notable  feature  of  the  onset  of  the  disease  is  its  suddenness,  and 
the  absence  of  any  premonitory  symptoms,  notably  the  rarity  of  a 
history  of  a  neglected  cold.  In  acute  cases,  a  fetid  purulent  discharge 
oozes  from  the  mouth  and  throat.  In  other  than  fulminating  cases, 
this  does  not  occur  until  about  the  third  day.  Transitory  aphonia  has 
been  observed,  but  in  this  case,  the  facial  and  hypoglossal  nerves  were 
also  involved.  Hoarseness  is  not  a  common  symptom,  the  pharynx 
and  larynx  as  a  rule  escaping.  A  shght  degree  of  bronchitis  exists  in 
a  small  proportion  of  cases.  In  very  acute  cases,  when  there  is  profound 
coma  and  marked  head  retraction,  ratthng  in  the  throat  and  coarse 
mucous  rales  are  present.  Such  cases  are  in  danger  of  suffocation, 
unless  the  throat  is  swabbed  out  frequently.  Broncho-pneumonia  is  a 
not  uncommon  comphcation  in  children,  and  occasionally  in  adults. 
The  meningococcus  has  been  stated  to  be  the  cause  of  this  comphcation. 
There  is,  however,  no  doubt  that  in  the  vast  majority  of  cases  the 
affection  is  pneumococcal.  The  growth  of  the  meningococcus  from  the 
sputum  does  not  prove  that  it  is  the  cause  of  the  lung  infection,  for  it 
may  have  been  derived  from  the  posterior  pharynx.  Lung  puncture 
is  the  only  method  of  substantiating  the  diagnosis.  On  the  few  occasions 
when  this  has  been  done,  the  pneumococcus  has  been  obtained.     Lobar 


n]  Symptoms  27 

pneumonia  is  an  uncommon  complication,  particularly  so  when  it  is 
remembefed  that  pneumonia  has  been  found  unduly  prevalent  at  the 
same  time  as  cerebio-spinal  meningitis.  Pleurisy  is  an  uncommon 
complication.  Mention  may  be  made  of  the  urgent  dyspnoea  which 
arises  in  fulminating  cases;  it  is,  indeed,  not  a  pulmonary  but  a 
nervous  symptom,  and  its  presence  is  of  the  gravest  import. 

In  considering  the  circulatory  symptoms,  it  may  be  noted  that  in 
fulminating  cases  the  extremities  are  cyanosed,  but  this  sign,  hke 
dyspnoea,  is  not  the  expression  of  cardiac  failure,  but  of  profoimd 
toxaemia,  combined  with  lack  of  adequate  aeration.  Endocarditis  is 
said  to  occur.  Myocarditis  leading  to  auricular  fibrillation  without 
valvular  change  occurred  in  one  of  our  cases.  The  previous  condition 
of  the  heart  in  this  case  was,  however,  doubtful.  From  the  point  of 
view  of  convalescence,  it  is  remarkable  what  httle  impress  a  disease  so 
acute  leaves  upon  the  circulatory  system  of  those  who  recover. 

Constipation  is  almost  the  invariable  rule.  Vomiting  at  the  outset 
may  be  replaced  by  diarrhoea.  One  case  under  our  care  was  seized  at 
the  seventh  day  with  mucous  diarrhoea,  going  on  to  the  stage  of  passing 
a  well-marked  intestinal  cast.  Otherwise  no  sequelae  are  to  be  appre- 
hended in  the  way  of  atonic  dyspepsia  and  other  digestive  troubles. 

Haematuria  may  occur  during  the  acute  stage,  even  without  the 
presence  of  a  purpuric  rash.  It  has  no  significance  with  respect  to  any 
further  renal  complications.  Sophian  found  pyelitis  in  .5  per  cent,  of 
cases  in  the  Texas  epidemic.  In  the  last  epidemic  in  England,  in  1915, 
this  complication  was  hardly  ever  observed.  In  view  of  the  extreme 
frequency  of  retention  and  overflow  incontinence,  any  observations  as 
to  the  source  of  pus  in  the  urine  would  require  most  searching  investi- 
gation. 


CHAPTER  III 

DIAGNOSIS 

Importance  of  early  diagnosis.  Early  signs,  indicating  lumbar 
puncture.  The  operation  of  lumbar  puncture.  Advisability  of 
anaesthesia.  Effect  of  puncture  on  blood  pressure.  Differential 
diagnosis  from  influenza,  from  pneumonia,  from  typhoid  fever, 
from  typhus  fever,  from  malignant  exanthemata,  from  tonsillitis  and 
pharyngitis,  from  tetanus,  from  tubercular  meningitis,  from  other 
forms  of  purulent  meningitis,  from  cerebral  abscess,  from  thrombosis 
of  lateral  sinus,  from  meningeal  haemorrhage,  from  poliomyelitis, 
from  acute  myelitis  and  from  delirium  tremens. 

The  value  of  a  diagnosis  is  largely  enhanced  when  it  leads  to  prompt 
and  efficient  treatment.  The  literature  of  earlier  epidemics  of  meningitis 
has  handed  down  a  store  of  clinical  observations  of  great  value,  whereby 
an  accurate  diagnosis  may  be  accomplished.  Such  a  diagnosis  is  based 
on  the  appearance  of  certain  symptoms,  on  their  relative  severity 
and  on  their  sequence  in  point  of  time.  It  must  be  stated  at  the  outset 
that  a  diagnosis  based  on  clinical  evidence  alone  cannot  be  conclusive, 
more  especially  in  the  early  stages.  As  will  be  shewn  later,  treatment  is 
capable  of  exerting  a  vital  effect,  and  the  date  at  which  it  is  begun 
is  of  great  moment.  Two  discoveries  of  recent  years  have  profoundly 
modified  the  outlook  as  to  early  diagnosis.  Of  these  the  first  was  the 
discovery  of  the  meningococcus  by  Weichselbaum  in  ]  887 ;  the  second 
the  introduction  of  lumbar  puncture  by  Quincke  in  1890.  With 
perfection  of  the  technique  of  lumbar  puncture  it  became  possible  to 
recover  the  meningococcus  from  the  cerebro-spinal  fluid  at  an  early 
stage  of  the  disease.  An  early  diagnosis  and  the  institution  of  specific 
treatment  are  thus  secured  by  one  and  the  same  procedure.  The 
question  to  be  determined,  therefore,  is  what  cardinal  symptoms  are 
sufficiently  suggestive  of  the  disease  to  justify  the  immediate  per- 
formance of  lumbar  puncture.  A  sudden  onset,  probably  accompanied 
bj'  a  rigor,  headache  gradually  increasing  in  intensity,  and  vomiting 
occurring  within  the  first  twenty-four  hours,  point  towards  meningitis, 
but  are  common  to  other  infections.    The  absence  of  herpes  or  a  macular 


OH.  Ill]  Diagnosis  29 

rash,  is  of  slight  value :  these  do  not  appear  until  the  third  to  fifth  day, 
and  to  wait  for  confirmation  from  their  appearance  might  mean 
fatal  delay.  The  presence  of  a  petechial  or  purpuric  rash,  which  may 
appear  in  the  first  twenty-four  hours,  leaves  so  little  doubt  as  to 
justify  immediate  lumbar  pimcture.  Haemophilia  must  be  excluded, 
as  lumbar  puncture  has  been  performed  on  a  case  of  this  disease  with 
meningeal  haemorrhage,  the  difficulty  in  arresting  bleeding  first  calling 
attention  to  the  true  nature  of  the  case.  Head  retraction  is  variable 
in  the  date  at  which  it  makes  its  appearance,  and  much  stress  should 
not  be  laid  on  its  absence.  The  cervical  muscles  should  be  carefully 
examined  for  any  tenderness  or  stiffness;  if  this  is  present,  the 
probability  in  favour  of  meningitis  is  increased.  The  value  of  Kernig's 
sign  in  all  adult  cases  cannot  be  over-estimated.  This  value  lies  firstly 
in  the  date  of  its  appearance, — it  may  be  only  slightly  marked  at  the 
end  of  eighteen  hours,  but  is  usually  fully  developed  at  the  end  of 
twenty-four;  and  secondly  in  the  fact  that  it  is  never  present  in  its  fidly- 
marked  form  in  other  affections  liable  to  be  mistaken  for  meningitis. 
Kernig's  sign  is  common  to  all  forms  of  meningitis  of  whatever  origin, 
but  its  presence  is  a  powerful  factor  in  determining  the  necessity  for 
immediate  lumbar  puncture.  Retention  of  urine  is  an  important 
symptom  to  be  taken  into  account.  It  occurs  in  a  large  proportion 
of  cases,  many  of  which  are  comparatively  mild  ones.  Further,  it 
may  make  its  appearance  at  the  end  of  twenty-four  hours,  and  is  an 
uncommon  symptom  at  this  early  stage  in  other  febrile  affections.  The 
presence  of  this  symptom  should  be  given  great  weight  in  estimating  the 
relative  values  of  the  clinical  aspects  of  the  case.  Early  delirium, 
especially  when  associated  with  the  persistence  or  indeed  aggravation  of 
the  headache,  tends  further  to  differentiate  the  case  from  other  acute 
infections.  To  sum  up:  a  patient  who  has  been  seized  with  sudden 
illness  ushered  in  by  a  rigor,  accompanied  by  severe  headache  rapidly 
growing  worse  and  soon  accompanied  by  vomiting,  may  be  regarded 
as  a  suspicious  case.  When  Kernig's  sign  is  present,  and  there  is  some 
pain  and  stiffness  of  the  muscles  of  the  neck,  and  if  retention  of  urine 
occurs,  the  probabilities  are  sufficiently  great  to  justify  lumbar  puncture. 
Delirium  going  on  to  coma,  the  presence  of  a  petechial  rash,  or  of 
head  retraction,  would  merely  confirm  these  probabilities. 

Before  discussing  the  differential  diagnosis  of  epidemic  meningitis, 
the  operation  of  lumbar  puncture  may  most  conveniently  be  described. 
Lumbar  puncture  was  first  performed  by  Corning,  in  America,  in 
1885    for    the    purpose    of    injecting    cocaine    into    the    theca.      In 


30  Diagnosis  [cii. 

1891  Wynter  published  four  cases  thus  treated  for  the  relief  of 
tubercular  meningitis.  Quincke  worked  out  the  technique  of  the 
operation,  and  it  is  largely  due  to  his  advocacy  that  it  has  come 
into  general  use.  The  anatomical  conditions,  which  make  lumbar 
puncture  possible,  are  the  width  of  the  inter-vertebral  foramina  in  the 
lumbar  region.  These  foramina  are  large  and  triangular  in  form, 
measuring  one-third  of  an  inch  across,  and  being  covered  in  by  the 
ligamenta  subflava.  Further,  below  the  fourth  lumbar  vertebra  the 
conus  medullaris  ceases,  and  the  vertebral  canal  is  occupied  only  by 
the  Cauda  equina.  By  traversing  a  comparatively  thin  layer  of  the 
lumbar  muscles,  it  is  thus  easy  to  pass  a  trocar  and  cannula  into  the 
spinal  canal  below  the  level  of  the  cord.  Considerable  diversity  of 
opinion  exists  as  to  the  advisability  of  giving  a  general  anaesthetic. 
The  American  writers,  Sophian  and  Heiman  and  Feldstein,  regard 
a  general  anaesthetic  as  entirely  unnecessary.  Sophian  has  advocated 
an  ingenious  method  of  distracting  the  patient's  attention  by  what  he 
terms  water  anaesthesia,  which  consists  in  the  patient  sucking  water 
through  a  straw  during  the  operation,  and  thus  distracting  his  attention. 
It  is,  of  course,  only  a  variant  of  the  old  naval  trick  of  biting  on  a 
bullet.  Robb,  who  has  tried  it  in  this  country,  has  been  disappointed 
with  its  efficacy.  Border  regards  general  anaesthesia  as  infinitely 
preferable  to  local,  an  experience  which  is  endorsed  by  Robb.  Our 
own  experience  is  entirely  in  favour  of  a  general  anaesthetic,  and  for 
the  following  reasons.  In  the  first  place,  it  is  obviously  necessary 
when  there  is  active  delirium;  it  would  be  impossible  to  keep  the 
patient  in  the  requisite  position  long  enough  to  perform  the  puncture 
and  run  off  the  full  quantity  of  fluid.  There  is,  moreover,  always  the 
very  definite  danger  of  the  patient  in  his  struggles  breaking  the  needle 
short  off  inside  the  vertebral  canal.  For  the  full  completion  of  the 
operation,  it  is  essential  that  as  much  fluid  as  possible  should  be  run 
ofl;  when  this  is  attempted  with  a  strugghng  patient,  the  result  is 
apt  to  be  an  object  lesson  in  the  futihty  of  half-measures.  A  further 
point  is  that,  when  lumbar  puncture  has  to  be  repeated  day  after  day, 
it  would  impose  an  entirely  unnecessary  strain  on  the  fortitude  of 
the  patient.  With  an  anaesthetic  patients  are  in  our  experience 
perfectly  willing  for  the  operation,  and  indeed  when  suffering  are  eager 
for  it.  When  headache  is  severe  it  is  no  uncommon  thing  to  see  a 
patient,  who  had  previously  been  restless  and  moaning,  pass  straight 
from  the  anaesthetic  to  a  peaceful  sleep  of  four  or  five  hours.  The 
argument  against  an  anaesthetic  is  naturally  that  it  is  exposing  the 


ni]  Diagnosis  31 

patient  to  a  further  danger,  which,  the  minor  character  of  the  operation 
does  not  warrant.  The  considerations  which  should  weigh  against  this 
view  have  been  stated.  Our  own  experience  was  that  in  276  successive 
lumbar  punctures  no  untoward  symptom  was  experienced  except  in 
two  cases.  One  of  these  was  a  case  of  multiple  cerebral  abscess  brought 
in  unconscious  but  restless,  in  which  respiratory  failure  occurred 
directly  after  the  evacuation  of  the  fluid.  The  probable  reason  for 
this  was  found  post-mortem  to  be  the  presence  of  a  large  cerebellar 
abscess,  which  the  withdrawal  of  fluid  allowed  to  press  on  the  floor 
of  the  fourth  ventricle.  Obviously,  death  in  this  case  can  hardly  be 
attributed  to  the  anaesthetic.  Another  case  of  pneumococcal  menin- 
gitis was  admitted  delirious  and  struggling,  and  died  of  respiratory 
failure  fifteen  minutes  after  the  operation.  In  both  these  cases,  lumbar 
puncture  was  imperative  and  in  both  its  performance  would  have  been 
impossible  without  an  anaesthetic.  With  these  two  exceptions  the 
operation  under  an  anaesthetic,  often  undertaken  when  the  patient's 
condition  seemed  desperate,  never  jier  se  gave  rise  to  a  single  untoward 
symptom.  In  all  ordinary  cases,  the  administration  of  a  general 
anaesthetic  would  appear  markedly  to  faciHtate  the  operation,  and 
to  be  practically  free  from  danger.  It  must  be  borne  in  mind  that  some 
acute  cases  die  of  sudden  respiratory  failure ;  and  the  fatal  event  might 
appear  to  be  hastened  by  the  administration  of  an  anaesthetic.  The 
general  restlessness  and  rigidity  of  the  lumbar  muscles  which  these 
patients  commonly  manifest  would  render  lumbar  puncture  a  very 
diflicult  matter.  Local  anaesthesia  in  our  own  hands  was  useless  in 
deUrious  cases,  and  did  not  obviate  rigidity  or  restlessness  in  mild 
ones.  Ether  is  on  theoretical  grounds  and  judged  by  practical  results 
the  best  anaesthetic.  Owing  to  the  open-air  wards  in  which  our  cases 
were,  the  chloroform  and  ether  mixture  was  found  more  convenient 
and  equally  safe.  Theoretically  the  increase  of  intracranial  pressure  due 
to  the  anaesthetic,  enables  more  complete  drainage  to  be  performed. 

Elaborate  apparatus  is  entirely  unnecessary  for  the  performance 
of  lumbar  puncture.  The  best  type  of  needle  is  that  devised  by 
Mr  Arthur  Barker.  It  has  the  merit  of  sufiicient  stiffness,  the  head 
is  of  good  size  and  fits  easily  into  the  palm  of  the  hand,  and  the  slot 
which  engages  the  trocar  is  easily  manipulated.  Should  no  special 
needle  be  available,  any  trocar  and  cannula  which  is  more  than  three 
inches  long  will  serve  perfectly  well.  The  trocar  must  be  sharp,  as 
with  a  blunt  point  there  is  always  the  danger  of  pushing  the  dura  mater 
in  front  of  the  needle.    The  instruments  should  be  boiled.    It  is  advisable 


32  Diagnosis  [ch. 

that  the  operator  should  wear  gloves.  The  skin  is  best  disinfected  by 
painting  with  iodine  or  by  washing  with  soap  and  water  and  rubbing 
with  ether  or  alcohol.  The  patient  should  be  placed  on  his  side,  so  that 
his  buttocks  are  just  at  the  edge  of  the  bed.  The  knees  are  then  flexed 
upon  the  abdomen  so  that  the  thighs  are  in  contact  with  the  abdominal 
wall.  The  head  and  trunk  are  bent  forward,  i.e.,  towards  the  centre 
of  the  bed,  and  all  pillows  are  removed  from  the  head  and  neck. 
By  this  manoeuvre  the  whole  spine  is  flexed,  the  inter-vertebral  foramina 
are  opened  to  their  fullest  extent,  and  the  ligamenta  subflava  are 
rendered  tense  and  more  easily  pierced.  The  exact  position  of  the 
patient  is  a  matter  of  great  importance,  and  one  of  the  main  sources 
of  failure  is  carelessness  in  this  respect.  The  puncture  should  be  made 
in  the  inter-vertebral  foramen  between  the  fourth  and  fifth  lumbar 
vertebrae.  The  spine  of  the  fourth  lumbar  vertebra  is  cut  by  a  vertical 
line  which  joins  the  summits  of  the  two  crista  ilii.  These  two  spots 
should  be  carefully  marked  out,  and  the  broad  flattened  spine  of  the 
fourth  lumbar  vertebra  will  be  readily  felt  in  the  line  which  joins  them. 
Below  the  spine  the  inter-spinous  space  will  be  felt,  varying  in  length 
from  half  an  inch  in  children  to  one  and  a  half  inches  in  adults.  The 
seat  of  puncture  having  been  determined,  the  theca  can  be  reached 
by  two  routes,  the  median  and  the  lateral.  The  merit  claimed  for 
the  median  operation  is  that  deviation  of  the  point  of  the  needle 
is  less  likely  to  occur  as  the  path  is  a  direct  one.  On  the  other  hand, 
in  adults  the  stout  inter-spinous  ligament  has  to  be  traversed,  an 
operation  which  seriously  interferes  with  the  tactile  sensations  of  the 
operator,  which  form  such  an  important  factor  in  the  success  of  the 
operation.  The  advantage  of  the  lateral  method  is  that  none  but 
soft  structures  are  traversed  until  the  ligamentum  subflavum  is  reached, 
thus  ensuring  greater  dehcacy  of  manipulation.  The  drawback,  as 
before  stated,  is  the  possibiHty  of  the  point  of  the  needle  being 
directed  at  a  wrong  angle,  an  initial  error  which  becomes  magnified 
as  the  depth  of  the  puncture  increases.  In  children  the  median 
operation  would  appear  to  be  the  more  easily  performed.  In  adults, 
however,  a  considerable  experience  amongst  soldiers  has  led  us  to 
the  conclusion  that  the  lateral  operation  confers  such  advantages  in 
the  way  of  delicate  manipulation  as  to  make  its  selection  advisable. 
The  lateral  operation  is  thus  performed:  the  needle  is  held  with  the 
butt  resting  in  the  hollow  of  the  palm,  the  shank  steadied  by  the 
forefinger  and  thumb.  A  point  is  then  selected  mid-way  between  the 
fourth  and  fifth  lumbar  spines,  a  quarter  of  an  inch  laterally  to  the 


Ill]  Diagnosis  33 

middle  line,  and  preferably  on  the  dependent  side.  The  skin  is  steadied 
by  the  forefinger  and  thumb  of  the  left  hand.  The  needle  is  pushed 
towards  the  middle  line,  forwards  and  shghtly  upwards.  Should  the 
needle  impinge  upon  bone,  it  must  be  slightly  withdrawn  and  the  point 
directed  lower  down.  If  no  bone  is  encountered,  the  point  of  the  needle 
is  felt  to  pass  through  the  ligamentum  subflavum,  which  gives  the 
sensation  of  piercing  gristle,  and  then  through  the  dura  mater.  The 
piercing  of  the  dura  mater  has  an  entirely  different  feel,  which  has  been 
described  as  being  like  passing  a  knitting  needle  through  sacking. 
When  the  dura  mater  has  been  pierced,  the  needle  can  be  felt  free 
in  the  theca.  If  the  point  is  still  further  pushed  on,  it  can  be  felt  to 
strike  the  body  of  the  vertebra,  a  manoeuvre  which  should  whenever 
possible  be  avoided,  on  account  of  the  danger  of  wounding  the  anterior 
longitudinal  veins.  The  depth  to  which  the  needle  must  be  introduced 
so  as  to  reach  the  theca  varies  from  three  inches  in  the  adult  to  one 
inch  in  children.  Methods  of  measuring  the  depth  to  which  the  needle 
penetrates  have  been  devised,  but  found  in  practice  to  be  an  entirely 
useless  encumbrance.  When  the  point  of  the  needle  can  be  felt  free 
in  the  theca,  the  trocar  should  be  withdrawn;  this  will  usually  be 
followed  by  a  flow  of  cerebro-spinal  fluid.  Should  no  fluid  flow,  the 
probability  is  that  the  needle  is  either  not  in  the  theca,  but  has  merely 
pushed  the  dura  mater  in  front  of  it,  or  has  struck  a  nerve.  The  trocar 
should  then  be  re-inserted,  and  the  needle  gently  moved  backwards 
and  forwards;  in  the  event  of  no  fluid  escaping  after  this  manoeuvre 
the  needle  must  be  withdrawn,  and  a  fresh  puncture  made  in  another 
place.  Except  in  advanced  hydrocephalic  cases,  there  is  probably  no 
such  thing  as  a  "dry  tap."  and  reaching  the  theca  is  only  a  matter  of 
perseverance.  The  same  cautions  apply  to  the  median  operation, 
except  that  the  puncture  is  made  directly  forwards  in  the  middle  hne. 
Those  who  are  performing  the  operation  for  the  first  time  should 
remember  that  the  operation  is  an  extremely  easy  one,  provided  first 
that  due  care  is  exercised  as  to  the  exact  position  of  the  patient,  and 
secondly  that  the  landmarks  are  accurately  ascertained.  Given  that 
these  two  requirements  are  satisfied,  very  little  manipulative  skill  is 
required  to  ensure  success.  As  the  fluid  escapes,  a  note  should  be 
made  of  the  pressure  at  which  it  flows  and  of  its  general  characteristics. 
Should  it  be  very  thick  and  purulent,  it  may  be  necessary  to  clear 
the  cannula  by  inserting  the  trocar.  After  the  first  few  drops  the  fluid 
should  be  collected  in  a  sterile  test  tube  for  bacteriological  examination. 
As  a  rule,  the  fluid  should  be  allowed  to  flow  until  it  reaches  the  normal 

F.  &  G.  3 


34  Diagnosis  [CH. 

rate,  which  is  estimated  at  one  drop  to  every  two  or  three  seconds. 
The  needle  is  then  gently  withdrawn,  and  the  puncture  covered  with 
gauze  and  collodion.  The  cUnical  experience  of  many  observers  has 
made  it  clear  that  the  removal  of  a  considerable  quantity  of  fluid 
is  not  attended  with  any  alarming  symptoms  from  the  sudden  lowering 
of  cerebro-spinal  pressure.  Manometers  have  been  devised  by  Quincke, 
Kroenig  and  Crohn,  whereby  the  decUne  in  cerebro-spinal  pressure 
may  be  gauged,  and  the  operation  stopped  in  case  of  any  sudden  fall. 
Careful  observations  as  to  pulse  and  respiration  in  some  hundreds 
of  operations  have  convinced  us  that  no  appreciable  shock  or  collapse 
is  met  with,  if  the  fluid  is  allowed  to  run  until  it  reaches  its  normal  rate. 

Sophian  gives  a  series  of  observations  on  the  changes  in  blood 
pressure  during  the  evacuation  of  cerebro-spinal  fluid.  In  two-thirds 
of  the  cases  the  blood  pressure  fell  from  3-10  millimetres  during  the 
operation ;  in  a  few  it  was  raised  2-12  milhmetres ;  in  the  rest  unchanged. 
Sophian  concludes  that  the  evacuation  of  fluid  in  considerable  quantity 
has  no  marked  effect  on  the  blood  pressure.  There  would  appear  to 
be  no  evidence  that  the  removal  of  large  quantities  of  fluid  by  lumbar 
puncture  is  attended  with  danger.  Some  observers  have  removed 
three  to  four  ounces.  We  have  constantly  removed  between  two  and 
three  oimces  without  the  appea.rance  of  any  symptoms  which  might 
cause  alarm. 

The  differential  diagnosis  of  cerebro-spinal  fever  is  mainly  concerned 
in  distinguishing  the  disease  from  acute  febrile  infections  on  the  one 
hand,  and  other  diseases  of  the  brain  and  meninges  on  the  other. 
The  chief  febrile  diseases  are  influenza  and  pneumonia,  while  the 
chief  cerebral  affections  are  meningitis  due  to  other  organisms,  and 
cerebral  abscess  multiple  or  single. 

The  diagnosis  of  early  cases  of  cerebro-spinal  fever  from  influenza 
presents  some  difficulty.  In  both  there  is  a  sudden  onset  accompanied 
by  headache  and  fever.  In  both  pain  and  stiffness  in  the  neck  as  well 
as  in  the  back  and  legs  are  prominent  symptoms.  In  cerebro-spinal 
fever  the  first  two  days,  even  of  an  attack  which  ultimately  becomes 
severe,  may  present  no  obvious  difference  from  those  of  a  case  of  influenza. 
The  points  to  be  noted  are  that  the  headache  in  cerebro-spinal  fever 
usually  increases  day  by  day,  and  when  vomiting  appears  a  day  or 
two  after  the  onset  without  diarrhoea,  the  case  may  be  regarded  as 
suspicious.  Gastric  influenza  is  rarely  unaccompanied  by  diarrhoea. 
In  influenza  again  search  for  Kernig's  sign  may  reveal  some  stiffness 
of  the  legs,  which  prevents  full  extension  of  the  knee.     Equivocal  as 


m]  Diagnosis  35 

this  sign  may  appear,  the  stiffness  of  influenza  remains  the  same  from 
day  to  day,  while  in  cerebro-spinal  fever  it  becomes  rapidly  more  marked 
until  the  fully-developed  Kernig  is  obtained.  Retention  of  urine  is 
in  favour  of  cerebro-spinal  fever.  The  most  likely  source  of  error  is 
that,  in  the  absence  of  an  epidemic  of  cerebro-spinal  fever,  the  latter 
disease  may  not  be  thought  of  until  a  marked  exacerbation  of  cerebral 
symptoms  occurs.  Much  valuable  time  may  thus  be  lost  before  treat- 
ment is  begun.  When,  on  reviewing  the  chnical  signs  and  symptoms, 
their  relative  value  appears  evenly  balanced,  lumbar  puncture  should 
be  performed.  In  this  connection  we  have  met  with  several  cases 
apparently  of  influenza,  in  which  the  severity  of  the  headache  appeared 
to  justify  lumbar  puncture.  Perfectly  normal  cerebro-spinal  fluid  was 
drawn  off,  which  however  ran  at  considerable  pressure,  with  remarkable 
relief  to  the  headache.  Mild  cases  of  cerebro-spinal  fever  may  be 
unrecognized,  and  classed  as  influenza,  but  no  proof  exists  that  the 
former  disease  is  ever  so  shghtly  marked  as  not  to  develop  at  least 
some  of  the  diagnostic  signs. 

At  the  onset  pneumonia  may  easily  be  confounded  with  cerebro- 
spinal fever.  This  is  notably  the  case  in  children  and  young  adults, 
in  whom  headache,  and  with  it  vomiting,  may  be  striking  symptoms 
in  the  first  few  days.  Physical  signs  are  usually  absent  at  this  stage. 
A  rise  in  the  pulse  respiration  ratio,  which  does  not  fluctuate  from 
hour  to  hour,  together  with  the  absence  of  Kernig's  sign,  are  all  in 
favour  of  pneumonia.  Should  physical  signs  of  consolidation  not 
appear,  and  the  cerebral  symptoms  tend  to  increase,  lumbar  puncture 
should  be  undertaken.  In  this  connection  we  would  point  out  that 
two  cases  have  been  admitted  into  our  ward  in  a  hydrocephalic  state, 
the  long-past  acute  stage  of  whose  disease  had  been  considered  through- 
out to  be  pneumonia.  The  meningococcus  was  proved  to  be  present 
in  both  by  lumbar  puncture. 

The  continuous  headache  and  fever  of  the  first  week  of  typhoid 
may  give  rise  to  some  doubt.  The  sudden  onset  of  meningitis  as 
compared  with  the  gradual  exacerbation  of  typhoid  are  points  to  be 
borne  in  mind.  Sir  William  Jenner  used  to  say,  "in  typhoid  headache 
ceases  when  delirium  begins,  whereas  in  meningitis  the  two  co-exist." 
This  clinical  fact  should  be  given  great  weight.  The  presence  of 
Kernig's  sign,  of  rigidity  of  the  neck,  and  possibly  of  bladder  symptoms 
would  help  in  decision.  It  is  very  rare  for  a  case  of  cerebro-spinal 
fever  to  remain  febrile  so  long  as  to  suggest  typhoid,  without  one  or 
other  of  these  symptoms  becoming  manifest.    The  characteristic  steady 

3—2 


36  Diagnosis  [ch. 

remittent  rise  of  typhoid  fever  is  hardly  ever  observed  in  cerebro- 
spinal fever.  In  the  latter  disease,  the  temperature  chart  is  usually 
very  irregular  and  frequently  intermittent.  After  the  first  week, 
Widal's  reaction  would  be  decisive. 

The  distinction  of  typhus  fever  from  cerebro-spinal  fever,  par- 
ticularly during  the  early  days,  is  a  matter  of  some  difSculty.  In 
both  there  is  a  sudden  onset  with  an  initial  rigor,  with  headache 
increasing  in  intensity  and  followed  by  delirium.  Retention  of  urine 
may  arise  early  in  typhus,  further  confusing  the  clinical  aspect  of  the 
case.  The  appearance  of  the  patient  presents  points  of  similarity;  in 
both  the  expression  may  be  dull  and  heavy,  with  that  curious  and 
haunting  expression  as  though  watching  a  phantasmagoria.  The 
points  of  difference  to  be  noted  are  that  delirium  comes  on  much 
later  in  typhus,  and  head  retraction  is  absent.  In  typhus  moreover 
the  pupils  are  contracted,  in  cerebro-spinal  fever  usually  dilated. 
A  petechial  rash  occurring  early  is  in  favour  of  cerebro-spinal  fever, 
when  appearing  later  its  significance  is  equivocal.  In  any  case  where 
the  symptoms  are  of  such  gravity  as  to  suggest  the  presence  of  typhus, 
the  point  should  be  settled  without  delay  by  lumbar  puncture  and 
bacteriological  examination. 

The  malignant  forms  of  scarlet  fever,  measles,  small-pox  and  mumps 
are  liable  to  be  confused  with  fulminating  cases  of  cerebro-spinal 
fever.  The  urgency  of  the  symptoms  would  point  to  immediate  lumbar 
puncture  as  the  only  method  of  estabUshing  a  diagnosis,  and  holding 
out  any  hope  of  benefit.  It  must  further  be  remembered  that  cerebral 
symptoms  may  occur  later,  in  both  measles  and  mumps.  This  complica- 
tion, however,  arises  late  rather  than  early  in  the  disease,  and  the 
previous  history  would  be  a  decisive  factor  in  forming  an  opinion. 

The  absence  of  proof  that  the  meningococcus  can  cause  an  acute 
affection  of  the  throat  has  already  been  insisted  upon.  But  as  this 
view  is  still  widely  held,  cases  of  tonsiUitis  and  pharyngitis  may  come 
under  observation  as  suspected  cerebro-spinal  fever.  Beyond  the 
frequently  severe  onset  with  rigor,  further  similarity  is  singularly 
lacking. 

An  attack  of  influenza,  pneumonia,  or  any  of  the  specific  fevers, 
may  be  followed  by  cerebro-spinal  fever  as  a  distinct  infection  during 
convalescence.  An  epidemic  of  measles  occurred  in  the  Highland 
Territorial  Division  in  the  Eastern  Counties  during  the  winter  of 
1914-15.  One  man  who  came  under  our  charge  had  been  afebrile 
for  sixteen  days  after  an  attack  of  measles;    he  suddenly  developed 


ni]  Diagnosis  37 

cerebral  symptoms,  from  -which  he  died.  The  meningococcus  was 
recovered  from  his  cerebro-spinal  fimd. 

The  common  presence  of  muscular  rigidity  and  some  degree  of 
opisthotonos  are  possible  sources  of  error  and  may  give  rise  to  a 
suspicion  of  tetanus.  In  tetanus,  however,  the  mind  is  absolutely  clear, 
and  the  general  constitutional  symptoms  are  slight.  Trismus  is 
extremely  rare  in  cerebro-spinal  fever,  its  absence  is  thus  a  diagnostic 
point  of  considerable  importance. 

The  main  difficulties  in  differential  diagnosis  are  met  with  in 
distinguishing  cerebro-spinal  fever  from  other  diseases  of  the  brain 
and  cord.  In  the  case  of  other  varieties  of  meningitis,  in  particular, 
the  pathological  condition  may  give  rise  to  symptoms  chnically 
identical  with  those  of  cerebro-spinal  fever.  Of  these  tubercular 
meningitis  is  far  the  commonest.  The  first  point  of  difference  to  be 
noted  between  the  two  diseases  is  the  character  of  the  onset.  The  onset 
of  tubercular  meningitis  is  marked  by  a  gradual  failure  of  health, 
accompanied  by  headache  slowly  increasing  in  intensity.  The  tempera- 
ture is  but  shghtly  raised,  and  photophobia  is  a  marked  symptom. 
In  cerebro-spinal  fever,  on  the  other  hand,  the  onset  is  sudden,  the 
temperature  is  raised,  the  headache  rapidly  increases  in  intensity  and 
dehrium  comes  on  early.  Photophobia,  common  in  tubercular  menin- 
gitis, is  rare  in  cerebro-spinal  fever.  Paralysis  of  one  or  other  of  the 
ocular  nerves  is  far  more  often  observed  in  tubercular  meningitis  than 
in  cerebro-spinal  fever.  A  definite  diagnosis  is,  however,  only  possible 
by  the  examination  of  the  cerebro-spinal  fluid.  The  fluid  in  tubercular 
meningitis  contrasts  with  that  of  cerebro-spinal  fever  in  the  com- 
paratively small  number  of  cells  present,  and  the  preponderance  of 
lymphocytes  which  form  70-100  per  cent,  of  the  total.  In  cerebro- 
spinal fever  the  lymphocytes  are  comparatively  few  in  number,  seldom 
amounting  to  30  per  cent.;  polymorphonuclear  cells  comprise  the  bulk 
of  the  deposit.  The  identification  of  the  meningococcus  in  film  or 
culture  clinches  the  matter.  The  fluid  from  a  hydrocephahc  case 
may  give  rise  to  considerable  difficulty,  if  the  case  has  not  come 
under  observation  in  the  acute  stage,  for  it  occasionally  happens 
that  the  cytological  picture  is  identical  with  that  of  tubercular 
meningitis.  The  cells  are  present  in  small  numbers,  the  lymphocytes 
form  70  per  cent,  or  more  of  the  total.  An  additional  difficulty  is  that 
the  detection  of  the  meningococcus  in  film  or  culture  is  often  impossible. 
The  identification  of  the  tubercle  bacillus  in  the  fluid  is  usually  a  matter 
of  extreme  difficulty,  consequently  its  absence  is  of  sHght  diagnostic 


38  Diagnosis  [cH. 

value.  The  diagnosis  between  the  hydrocephalic  stage  of  cerebro- 
spinal fever  and  tubercular  meningitis  may  therefore  rest  entirely  on 
the  pre^dous  history  and  the  nature  of  the  onset. 

Purulent  meningitis  may  occur  as  the  result  of  infection  by  any 
of  the  pyogenic  group  of  bacteria.  The  pneumococcus  is  one  of  the 
commonest  causes  of  a  primary  meningitis  of  this  kind.  The  chnical 
signs  are  largely  identical  with  those  of  cerebro-spinal  fever,  except 
that  the  course  and  development  of  symptoms  proceed  at  a  more 
rapid  rate  than  in  the  latter  afiection.  This  rapid  march  of  symptoms, 
coupled  with  their  extreme  gravity,  renders  lumbar  puncture  imperative, 
without  waiting  for  any  further  developments  to  aid  in  diagnosis. 
Pneumococcal  meningitis  is  usually  secondary  to  a  pneumococcal  in- 
fection elsewhere,  it  may  be  in  the  lung  or  middle  ear,  but  may  also  form 
part  of  a  general  primary  pneumococcal  septicaemia.  In  long-standing 
hydrocephalic  cases  of  cerebro-spinal  fever  there  may  be  a  secondary 
terminal  infection  by  the  pneumococcus.  The  onset  of  streptococcal 
meningitis  is  often  somewhat  obscured,  as  meningitis  is  usually  secondary 
to  a  focus  of  infection  elsewhere,  most  commonly  about  the  middle 
ear.  The  course  is  more  rapid  than  that  of  cerebro-spinal  fever.  The 
symptoms  are  those  of  spinal  meningitis  in  general,  and  a  diagnosis  can 
only  be  arrived  at  by  bacteriological  examination  after  lumbar  puncture. 
Staphjdococcal  meningitis  is  very  rare,  when  it  occurs  the  symptoms 
are  those  of  spinal  meningitis  and  are  indistinguishable  chnically  from 
those  of  cerebro-spinal  fever.  Lumbar  puncture  and  bacteriological 
examination  afford  the  only  means  of  ascertaining  the  infecting 
organism.  The  course  of  the  disease  is  very  rapid,  lasting  from  three 
to  five  days,  and  leading  invariably  to  a  fatal  result.  The  meninges 
in  this  infection  are  involved  secondarily  to  some  focus  existing  else- 
where in  the  body.  One  case  which  came  imder  our  care  was  admitted 
with  all  the  symptoms  of  cerebro-spinal  fever;  staphylococcus  aureus 
was  grown  from  the  lumbar  puncture  fluid.  Post-mortem  marked 
purulent  meningitis  was  found.  Cultures  of  the  heart's  blood,  the 
meninges,  the  lung  and  the  pleura  all  grew  a  pure  culture  of  staphy- 
lococcus. The  only  source  of  this  general  staphylococcal  septicaemia 
was  a  small  ulcer  in  the  anterior  fold  of  the  axilla. 

Cerebral  abscess  may  give  rise  to  symptoms  closely  simulating  those 
of  cerebro-spinal  fever.  Such  abscesses  may  be  single  or  multiple. 
The  solitary  abscess  is  usually  associated  with  disease  of  the  middle  ear. 
The  onset  is  sudden  and  is  characterized  by  headache  and  vomiting, 
accompanied  by  fever.     The  headache  in  cerebral  abscess  is  usually 


in]  Diagnosis  39 

unilateral  and  tends  to  lessen  in  intensity,  in  contradistinction  to  that 
in  epidemic  meningitis,  which  increases  in  severity.  Optic  neuritis  is 
frequent  in  cerebral  abscess,  rarely  observed  in  cerebro-spinal  fever. 
The  presence  of  any  local  affection  of  the  ear  is  strongly  in  favour  of 
cerebral  abscess.  The  differential  diagnosis  becomes  exceptionally 
difficult  if  the  cerebral  abscess  spreads  to  the  base  of  the  brain  and  down 
the  cord.  Lumbar  puncture  then  yields  a  purulent  fluid,  resembhng 
closely  that  obtained  in  cerebro-spinal  fever.  Such  a  combination  of 
lesions  reproduces  accurately  the  symptoms  of  the  latter.  The  presence 
of  Kernig's  sign  under  these  circumstances  renders  diagnosis  by 
other  than  bacteriological  means  sometimes  impossible. ,  A  case  came 
under  our  care  in  which  no  external  signs  of  ear  disease  were  present, 
and  lumbar  puncture  yielded  a  purulent  fluid  at  considerable  pressure. 
No  organisms  were  identified  with  certainty  in  films,  and  no  growth 
was  obtained  in  culture,  though  three  separate  puncture  fluids  were 
sown.  It  was  therefore  thought  possible  that  the  patient  was  suffering 
from  cerebro-spinal  fever  due  to  a  meningococcus  which  was  difficult 
to  grow  on  artificial  media.  Post-mortem  there  was  a  simple  abscess 
in  the  temporo-sphenoidal  lobe,  with  necrosis  of  the  petrous  portion  of 
temporal  bone.  The  abscess  had  spread  to  the  base  of  the  brain, 
and  a  purulent  meningitis  was  present  here  and  throughout  the  length 
of  the  cord  (Plate  X,  fig.  4).  Film  preparations  from  the  abscess 
shewed  streptococci  in  short  chains  and  fusiform  bacilli.  Neither  of 
these  organisms  could  be  grown,  though  various  media  were  tried. 
The  simulation  of  cerebro-spinal  fever  is  thus  practically  complete  in 
a  case  of  this  kind.  Multiple  abscesses  of  the  brain  are  frequently 
secondary  to  septic  injuries  under  the  aponeurosis  of  the  scalp.  Such 
a  condition  gives  rise  to  symptoms  which  are  chnically  indistinguish- 
able from  those  of  soHtary  abscess.  In  a  case  under  our  care,  the  only 
external  sign  of  injury  was  a  small  locahzed  swelhng  lying  deep  to 
the  occipital  muscle. 

Thrombosis  of  the  lateral  sinus  also  gives  rise  to  acute  cerebral 
symptoms.  The  character  of  the  temperature  and  the  constant 
repetition  of  rigors  are  usually  sufficiently  marked  to  indicate  the 
pyaemic  nature  of  the  condition. 

Meningeal  haemorrhage  may  present  such  similarity  to  cerebro- 
spinal fever  as  to  make  its  exclusion  a  matter  of  some  difficulty. 
A  history  of  coma  without  previous  delirium  or  an  initial  rigor  would 
exclude  all  but  fulminant  cases  of  cerebro-spinal  fever,  whose  recognition 
should  present  no  difficulty.     A  raised  temperature  is  in  favour  of 


40  Diagnosis  [ch.  hi 

cerebro-spinal  fever.  The  presence  of  hemiplegia  at  so  early  a  stage 
would  be  in  favour  of  meningeal  haemorrhage. 

Poliomyehtis  may  occasionally  present  some  difficulty  in  children. 
As  a  rule,  the  constitutional  disturbance  is  so  shght  and  the  palsy 
becomes  manifest  so  soon  as  to  make  the  distinction  easy.  In  the  more 
acute  form,  which  is  often  epidemic,  the  onset  may  simulate  cerebro- 
spinal fever.  The  early  occurrence  of  locaUzed  palsies  or  of  hemiplegia 
is  the  chief  distinguishing  point.  In  the  cerebral  type  known  as 
pohoencephahtis  these  may,  however,  be  absent.  The  latter  form  is 
invariably  ushered  in  by  a  convulsion,  which  is  a  comparatively  un- 
common event  in  cerebro-spinal  fever.  In  cases  of  doubt,  the  diagnosis 
can  be  determined  by  bacteriological  examination  of  the  lumbar 
puncture  fluid.  Acute  anterior  poliomyelitis  has  a  seasonal  prevalence 
very  different  from  that  of  epidemic  meningitis,  occurring  chiefly  in  the 
summer  and  autumn. 

Acute  myehtis,  if  accompanied  by  fever,  may  be  mistaken  for 
cerebro-spinal  fever.  But  the  complete  absence  of  cerebral  symptoms 
and  the  presence  of  signs  of  localizing  lesions  in  the  cord  renders 
differentiation  easy. 

Cerebro-spinal  fever  in  the  acute  stage  may  be  mistaken  for  delirium 
tremens.  A  careful  examination  will  shew  signs  of  definite  affection 
of  the  nervous  system  in  cerebro-spinal  fever,  which  will  suffice  to 
differentiate  the  two  conditions. 


CHAPTER   IV 

ACUTE   FORMS 

Classification.  Fulminating  form,  an  acute  meningitis  not  a  septi- 
caemia. Netter's  ambulatoi'y  type,  Sophian's  accumulative  stage. 
Acute  fatal  type.    Acute  type  with  recovery.    Abortive  forms. 

The  acute  onset  of  cerebro-spinal  fever  has  already  been  described, 
and  is  to  a  greater  or  less  degree  practically  universal.  The  subsequent 
course  varies,  but  allows  of  a  rough  separation  of  cases  into  two  classes ; 
the  acute,  in  which  either  death  occurs  or  the  patient  is  on  the  way 
to  convalescence  in  about  a  fortnight,  and  the  sub-acute  and  chronic, 
in  which  the  issue  is  in  doubt  for  a  longer  period.  The  acute  class  will 
be  dealt  with  in  four  categories : 

Fulminating ; 

Acute  fatal  cases; 

Acute  cases  which  recover; 

Abortive  cases. 
The  name  fulminating  or  foudroyant  has  been  apphed  to  those 
cases  which  begin  with  startling  suddenness  and  run  a  uniformly 
rapid  course  terminating  in  death  in  twenty-four  to  thirty-six  hours. 
The  whole  aspect  of  these  cases  is  one  of  a  profound  toxaemia,  analogous 
to  the  mahgnant  forms  of  the  acute  exanthemata,  and  recalUng  \ividly 
the  hterary  descriptions  of  plague.  The  onset  may  be  startHngly 
sudden,  in  some  cases  the  patient  falls  down  in  the  street,  and  is 
picked  up  comatose.  A  man  may  be  in  his  ordinary  health  the  night 
before,  and  be  found  unconscious  or  even  dead  in  bed  in  the  morning. 
The  onset  is  occasionally  marked  by  a  convulsion,  and  convulsions  may 
occur  during  the  brief  course  of  the  disease.  More  often  there  is  a 
rigor  followed  immediately  by  intense  headache  and  vomiting,  this 
again  rapidly  succeeded  by  dehrium  passing  quickly  into  coma,  the 
whole  sequence  of  these  events  occupying  only  four  or  five  hours. 
The  stage  of  delirium  may  last  longer  and  assume  a  violent  or  even 
maniacal  form  before  coma  supervenes.  Vomiting  occurs  in  those 
cases  in  which  consciousness  is  not  lost  at  the  onset.     Within  a  few 


42  Acute  Forms  [CH. 

hours  a  true  purpuric  haemorrhagic  rash  may  make  its  appearance. 
The  blotches  may  be  as  big  as  a  plum,  and  are  scattered  indiscriminately 
over  the  body,  the  face  being  frequently  involved;  they  are  usually 
of  a  deep  grape  colour,  and  may  occasionally  take  on  a  bullous 
character.  Plate  IV,  taken  from  a  case  which  died  within  twenty- 
four  hours  of  being  found  unconscious  in  bed,  well  illustrates  this 
purpuric  rash.  In  other  cases  a  petechial  rash  appears  early,  distributed 
over  points  of  pressure.  The  face  may  be  either  pale  or  cyanotic 
and  bathed  in  sweat;  the  hands  are  blue  and  tremulous.  Subsultus 
tendinum  is  usually  present.  Dyspnoea  is  a  striking  symptom;  the 
respirations  are  rapid  and  shallow,  while  the  patient  beats  the  air 
with  his  hands  in  a  vain  struggle  for  breath.  The  respiration  may 
assume  the  Cheyne-Stokes  rhythm.  The  temperature  is  usually  not 
markedly  raised,  being  under  100  or  sometimes  subnormal.  The  pulse  is 
feeble  and  fluttering,  quickened  not  slowed,  and  may  be  irregular. 
There  is  always  retention  of  urine.  Head  retraction  and  muscular 
rigidity  are  generally  absent;  it  would  appear  that  the  disease  kills 
the  patient  before  these  signs  have  time  to  develop.  On  the  other 
hand  Kernig's  sign  is  generally  present  even  at  an  early  stage.  Netter 
calls  attention  to  the  possible  medico-legal  aspect  of  these  cases. 
Thus  a  patient  suddenly  attacked  may  fall  in  the  street  and  fracture 
his  skull,  a  source  of  confusion  which  should  be  borne  in  mind.  The 
occurrence  of  vomiting,  followed  by  rapidly  oncoming  coma,  may  again 
give  rise  to  suspicions  of  poisoning.  A  careful  estimate  of  the  symptoms 
and  signs  should  avoid  error  in  this  regard. 

Considerable  diversity  of  opinion  has  been  expressed  as  to  the 
nature  of  this  form  of  the  disease.  It  is  held  by  some  that  it  is  essentially 
an  invasion  of  the  blood  by  the  meningococcus,  a  true  meningococcal 
septicaemia.  Others  again  maintain  that  death  is  brought  about  by 
the  intensity  of  the  meningeal  inflammation.  That  a  true  meningococcal 
septicaemia  can  occur  is  proved  by  a  case  reported  by  Andrewes  in 
1906.  A  medical  man  was  attacked  with  symptoms  of  fulminant 
purpura.  Blood  examined  in  film  preparations,  drawn  from  the  basilic 
vein  shortly  before  death,  was  found  to  contain  large  cocci  exclusively 
intracellular,  enclosed  in  pairs  or  groups  of  half-a-dozen,  rarely  more, 
in  the  polynuclear  leucocytes.  The  blood  yielded  a  pure  culture  of  a 
gram  negative  coccus,  which  examination  proved  to  be  identical  with 
the  meningococcus.  This  patient  exhibited  no  symptoms  of  meningitis 
during  life,  and  post-mortem  there  was  no  evidence  of  meningitis  even 
on    microscopical    examination;     there    were    haemorrhages    in    the 


rv]  Acute  Forms  '  43 

sub-arachnoid  space  as  elsewhere.  This  case  estabhshes  beyond  doubt 
the  occurrence  of  a  true  meningococcal  septicaemia. 

Netter  refers  to  cases  in  which  the  cerebro-spinal  fluid  is  clear,  and 
in  which  post-mortem,  beyond  marked  engorgement  of  the  vessels,  the 
meninges  appear  normal,  with  the  exception  that  the  pia  mater  at  the 
level  of  the  cisterna  pontis,  is  opalescent  and  lustreless.  jMicroscopical 
examination  of  the  meninges  at  this  level  shews  a  polynuclear  infiltration 
and  meningococci.  Netter  regards  these  cases  as  shewing  that  the 
patients  were  killed  by  septicaemia  before  the  pathological  lesions  of 
the  brain  had  time  to  become  fully  developed.  Cases  presenting  such 
pathological  conditions  he  names  true  fulminating  cases,  as  opposed 
to  those  in  whom  purulent  meningitis  is  found,  which  are  classified  as 
ambulatory  cases  with  a  terminal  fulminating  stage.  In  this  con- 
nection it  may  be  pointed  out  that  the  naked  eye  appearance  of  the 
cerebro-spinal  fluid  is  a  fallacious  guide  to  its  pathological  properties. 
Examination  of  a  centrifugalized  fluid  will  often  materially  alter  the 
evidence  furnished  by  naked  eye  inspection  alone.  Sophian  conceives 
that  during  the  earlier  hours  of  the  disease  the  meningococcus  is 
circulating  in  the  blood  stream,  before  ahghting  on  the  meninges  and 
setting  up  an  inflammatory  process.  This  phase  he  designates  the 
"accumulative  stage."  No  clinical  or  pathological  evidence  is  adduced 
in  support  of  this  view,  and  the  observations  from  other  sources  are 
so  conflicting  that  the  common  occurrence  of  such  a  stage  remains 
a  matter  of  theory.  The  evidence  in  favour  of  a  true  septicaemia  is 
based  on  one  undoubted  case  of  Andrewes',  and  Netter's  cases  in 
which  death  occurred  before  meningitis  had  reached  a  purulent  stage. 
A  few  similar  cases  have  also  been  reported  from  Germany. 

Other  pathological  observations,  however,  put  a  different  aspect  on 
the  question.  Purulent  meningitis  may  be  observed  in  cases  which  have 
been  fatal  at  a  very  early  stage.  Netter  speaks  of  the  astonishment  with 
which  he  has  viewed  the  purulent  aspect  of  the  meninges,  in  contrast 
with  the  short  duration  of  the  symptoms.  In  our  own  experience  we 
have  foimd  purulent  cerebro-spinal  fluid  five  hours  after  the  patient  had 
been  found  imconscious  in  bed.  In  this  case,  in  which  the  patient  died 
in  twenty-four  hours  from  the  time  of  being  found  unconscious,  there 
was  well-marked  purulent  meningitis  of  the  vertex  and  cord.  Another 
case  yielded  purulent  cerebro-spinal  fluid  at  the  end  of  twenty-four 
hours,  and  well-marked  purulent  meningitis  was  foimd  at  the  end  of 
thirty-six  hours.  In  a  third  case,  which  was  found  dead  in  bed,  purulent 
meningitis  was  found  post-mortem.     As  this   man   had   been  doing 


44  Acute  Forms  [ch. 

duty  the  night  before,  the  whole  course  of  the  disease  cannot  have 
been  more  than  twelve  hours,  and  yet  in  this  short  time  the  essential 
anatomical  lesion  of  the  disease  had  been  evolved.  Netter  explains 
these  cases  on  the  hypothesis  that  they  are  ambulatorv  cases  with  a 
fulminating  terminal  stage.  This  author  contrasts  these  with  the 
septicaemic  type  presenting  slight  meningeal  changes,  wliich  he  regards 
as  the  true  fulminating  type  of  the  disease,  while  the  ambulatory  cases 
are  but  its  cHmcal  coimterfeit.  The  theory  of  an  ambulatory  stage 
would  require  a  considerable  weight  of  ehnical  observation  to  sub- 
stantiate it.  which  is  hitherto  lacking.  There  are  moreover  reasons  for 
doubting  its  probable  existence.  In  the  first  place  a  notable  feature 
of  cerebro-spinal  fever  is  its  sudden  onset  in  persons  who  appeared 
to  be  in  their  ordinary  health.  A  review  of  the  histories  of  a  con- 
siderable number  of  cases  reveals  no  prolonged  period  of  malaise  in 
any  way  comparable  to  the  ambulatory  form  of  typhoid.  Further 
all  the  fulminating  cases,  which  came  under  our  care  or  witliin  ovii 
knowledge, .  were  at  duty  within  a  few  hovirs  of  being  attacked. 
The  conclusion  would  appear  to  be  that  in  the  majority  of  cases,  at 
all  events,  the  meningococcus  is  capable  of  producing  the  essential 
anatomical  lesions  of  the  disease  in  a  siirprisingly  rapid  manner.  From 
this  it  would  be  fair  to  asstune  that  death  is  due  rather  to  the  intensity 
of  the  pathological  process  than  to  any  general  infection  of  the  blood 
stream. 

The  view  that  we  are  at  present  inclined  to  uphold  is  that  the 
true  fulminating  tA'pe  of  the  disease,  as  most  commonly  met  with, 
is  an  acute  and  very  violent  form  of  a  true  infection  of  the  cerebro- 
spinal system.  A  septicaemic  form  of  meningococcal  infection  does 
occur  rarely,  but  it  essentially  differs  both  clinically  and  pathologically 
in  furnishing  no  evidence  of  disease  of  the  meninges  of  the  brain  and 
cord.  Again,  in  the  septicaemic  form  the  cocci  can  easily  be  found 
in  the  blood,  while  in  the  fulminating  form  of  meningitis  positive  blood 
cultures  can  only  occasionally  be  obtained  with  great  difficulty. 

In  the  acute  fatal  type  the  onset  is  sudden,  the  usual  history  is 
of  a  feeling  of  indisposition  with  distaste  for  food,  which  may  last  for 
an  hour  or  two  and  is  then  followed  by  a  rigor.  With  or  even  before 
the  rigor  headache  begins  and  rapidly  increases  in  intensity.  The 
temperattire  rises  to  101-103  and  with  varying  remissions  remains  at 
this  level.  Within  the  first  twelve  hours  vomiting  occurs;  this  may 
be  only  transitory,  or  be  continuous  and  very  distressing.  Xausea 
is  usually  not  a  marked  symptom.    In  from  twelve  to  thirty-six  hours 


iv]  Acute  Forms  45 

delirium  begins.  This  at  first  is  not  continuous,  but  mainly  nocturnal, 
and  the  patient  can  usually  answer  a  question  perfectly  sensibly. 
As  dehrium  becomes  more  marked,  the  patient  becomes  restless, 
constantly  fumbhng  with  his  hands  and  trying  to  get  out  of  bed. 
During  the  second  day,  mere  muttering  may  give  place  to  noisy  and 
sometimes  maniacal  delirium.  In  the  course  of  the  second  day  a 
petechial  rash  may  make  its  appearance,  distributed  over  points  of 
pressure,  such  as  the  knees,  elbows,  shovilders  and  malleoU.  The 
appearance  of  this  rash  is  evidence  of  a  severe  toxaemia,  to  -which 
doubtless  some  of  the  cerebral  manifestations  are  due.  The  presence 
in  the  post-mortem  room  of  particularly  dense  collections  of  pus, 
which  during  life  have  given  rise  to  a  definite  train  of  nervous  symptoms 
such  as  localized  convulsions  or  hemiplegia  (Plate  VII),  suggest  that  the 
toxic  effect  from  the  exudate  on  the  subjacent  nervous  tissue  is  severe. 
In  addition,  however,  the  increased  intracranial  pressure  plays  a  part 
in  the  production  of  the  symptoms.  An  evanescent  erythematous  rash 
may  appear  at  any  time  in  the  course  of  acute  symptoms.  At  the  same 
time  pain  and  tenderness  at  the  back  of  the  neck  are  noticeable,  and 
head  retraction  begins  to  develop.  Kernig's  sign  can  usually  be  obtained 
early  in  the  second  day.  During  the  second  or  third  day  retention  of 
urine  occurs  in  a  considerable  number  of  cases.  The  symptoms  during 
the  second  day  may  not  only  have  undergone  no  aggravation,  but 
may  even  considerably  diminish  in  intensity.  A  recognition  of  this 
is  a  matter  of  the  utmost  importance  as  the  apparent  amehoration 
may  seem  to  warrant  a  purely  expectant  attitude.  The  postponement 
of  lumbar  puncture  at  this  stage  may  determine  the  ultimate  issue  of 
the  case  unfavourably.  With  the  beginning  of  the  third  day  a  definite 
.  change  takes  place ;  the  muttering  delirium  gives  place  to  profound 
coma,  or  to  maniacal  delirium  with  great  restlessness,  head  retraction 
is  increased,  retention  of  urine  is  complete.  At  the  same  time  the 
respiration  is  frequently  hurried  and  irregular  in  rhythm.  This 
irregularity  may  present  the  imdulatory  type  in  which  paroxysms  of 
rapid  or  shallow  breathing  alternate  at  longer  or  shorter  intervals 
with  the  normal  respiratory  rhythm.  Another  type  of  respiratory 
irregularity  is  that  associated  with  the  name  of  Biot,  which  is 
characterized  by  periods  of  apnoea  which  occur  at  varying  intervals. 
Deep  sighing  is  most  commonly  observed  accompanying  this  type. 
Biot's  type  of  breathing  is  a  famiUar  phenomenon  in  tubercular 
meningitis,  its  occurrence  in  cerebro-spinal  fever  is  of  equally  grave 
import.     Connor  and  Stillman  took  tracings  from  several  himdreds 


46  Acute  Forms  [ch. 

of  cases  suffering  from  different  diseases,  and  in  only  one  case 
suffering  from  meningitis  was  this  form  of  arhythmia  observed. 
Cheyne-Stokes  breathing  is  not  usually  observed  except  at  the  near 
approach  of  death.  The  cerebro-spinal  fluid  at  this  stage  always  runs 
at  high  pressure,  and  is  usually  purulent  in  appearance;  its  micro- 
scopical characters  are  described  elsewhere.  With  this  deepening 
coma  occurring  on  the  third  or  fourth  day  there  may  be  mucus  rattling 
in  the  throat,  partly  due  to  coma,  but  probably  also  to  the  position 
of  the  windpipe,  owing  to  the  extreme  retraction.  A  fetid  discharge 
may  ooze  from  the  mouth  and  nose.  In  some  cases  the  power  of 
swallowing  is  entirely  lost,  while  in  others  it  is  retained.  Incontinence 
of  urine  and  faeces  may  occur,  but  more  commonly  there  is  absolute 
constipation  and  retention  of  urine.  With  the  advent  of  the  fourth 
day  the  symptoms  assume  a  still  graver  aspect.  The  coma  deepens, 
the  breathing  becomes  more  hurried,  the  hands  are  cyanotic,  and 
the  body  is  often  bathed  in  sweat.  Herpes  may  appear  on  the  lips 
or  elsewhere  on  the  fourth  day,  and  a  macular  rash  on  the  extremities, 
though  this  is  an  uncommon  phenomenon  in  fatal  cases.  Convulsions 
may  appear  at  this  stage,  or  hemiplegia  become  manifest:  both 
phenomena  are  found  associated  with  locahzed  purulent  deposits  on 
the  cortex  leading  to  compression.  The  aggravation  of  symptoms 
on  the  third  day  cannot  be  due  merely  to  an  increased  toxaemia, 
but  is  to  be  explained  by  the  establishment  of  compression  of 
vital  nervous  structures  by  increased  intracranial  pressure.  Lumbar 
puncture,  with  the  removal  of  large  quantities  (two  ounces  or  more)  of 
cerebro-spinal  fluid  or  with  the  injection  of  serum,  brings  no  alleviation 
of  the  symptoms.  In  our  experience  lumbar  puncture  was  rarely 
performed  in  these  cases  before  the  third  day,  owing  to  the  difficulty  ■ 
of  getting  the  patients  sent  to  hospital  from  billets  earlier.  Lumbar 
puncture  was  thus  undertaken  at  a  period  when  as  a  rule  the  symptoms 
had  shewn  a  marked  and  comparatively  sudden  aggravation.  Arguing 
from  the  success  attending  this  operation  in  other  cases,  it  is  fair  to 
assume  that,  if  pressure  had  been  relieved  before  compression  had 
become  estabhshed,  alleviation  and  in  some  cases  cure  might  have  been 
the  result.  When  drainage  by  puncture  has  been  attempted  and  failed 
to  give  relief,  the  subsequent  progress  of  the  case  is  uniformly  towards 
a  fatal  issue.  The  symptoms  are  mainly  respiratory  with  dyspnoea 
and  rapid  shallow  breathing,  the  patient's  hands  meanwhile  beating 
the  air;  or  again  Cheyne-Stokes  breathing  may  make  its  appearance. 
In  some  cases  the  patient  dies  of  true  respiratory  failure,  the  respiration 


iv]  Acute  Forms  47 

ceasing  suddenly,  and  the  patient  becoming  cyanosed,  while  the  heart 
continues  beating  long  after  respiration  has  ceased.  The  temperature 
may  rise  to  105  or  more  before  death. 

The  symptoms  in  the  acute  type  of  case,  in  which  recovery  takes 
place,  as  a  rule  resemble  those  of  the  fatal  cases  though  in  a  some- 
what minor  degree.  In  rare  instances  the  onset  presents  a  striking 
similarity  to  that  of  a  fulminating  case.  An  officer's  servant  was 
admitted  to  the  First  Eastern  Hospital  having  been  found  unconscious 
in  bed  at  2  a.m.  He  had  been  at  his  duties  the  night  before,  and  had 
not  complained  of  ill  health.  On  admission,  he  was  profoundly  comatose, 
with  twitching  of  the  limbs,  nystagmus,  and  retraction  of  the  head. 
There  was  retention  of  urine  and  the  patient  was  unable  to  swallow. 
The  temperature  was  subnormal,  and  the  pulse  slow  and  intermittent. 
Lumbar  pvincture  was  performed  fourteen  hours  after  onset,  an  ounce 
of  purulent  fluid  containing  meningococci  being  removed.  The  next 
day  he  was  somewhat  better;  another  ounce  of  purulent  fluid  was 
removed  by  lumbar  pimcture.  On  the  third  day  he  was  able  to  swallow ; 
the  theca  was  again  tapped,  an  ounce  of  purulent  fluid  being  removed. 
From  this  date  he  made  an  uninterrupted  recovery,  being  discharged 
on  the  eighteenth  day.  A  macular  reddish  purple  rash  made  its 
appearance  on  the  fourth  day,  distributed  over  the  abdomen,  fore-- 
arms  and  legs.  With  the  exception  of  the  absence  of  dyspnoea  and  a 
purpuric  rash,  the  earlier  clinical  features  in  this  case  bore  a  close 
resemblance  to  those  observed  in  the  fulminating  type  of  the  disease. 
The  initial  symptoms  in  this  case  are,  however,  quite  exceptional: 
as  a  rule  the  march  of  the  disease  is  slower  and  milder  in  character. 
The  onset  is  marked  by  a  sudden  feehug  of  indisposition,  the  patient 
often  being  able  to  determine  precisely  the  place  and  hour  where  he 
first  experienced  it.  According  to  some  authors,  the  onset  may  have 
been  preceded  by  coryza  or  a  sore  throat;  but  in  our  experience  such 
immediate  prodromal  symptoms  were  conspicuously  absent.  This 
feeling  of  indisposition  is  accompanied  by  complete  anorexia,  and  is 
followed  in  two  or  three  hours'  time  by  shivering  which  usually  takes 
the  form  of  a  definite  rigor.  The  temperature  rises  rapidly  to  102-103; 
the  pulse  is  somewhat  quickened,  the  respirations  are  only  very  slightly 
accelerated.  Even  before  the  initial  rigor  headache  begins  and  gradually 
increases  in  intensity,  usually  accompanied  by  vomiting  within  the 
first  twenty-four  hours.  Delirium  may  be  present  during  the  first 
day,  but  usually  appears  later.  After  this  sudden  onset  the  second 
day  may  be  charactei-ized  by  no  marked  accentuation  of  symptoms 


48  Acute  Forms  [ch. 

or  even  by  some  amelioration,  "the  period  of  bailing  symptoms"  of 
the  French  authors.  A  careful  survey  of  the  signs  and  symptoms  at 
this  stage  is  of  great  importance,  as  it  may  enable  treatment  to  be 
instituted  at  once.  Kernig's  sign  is  usually  present,  and  careful  examina- 
tion of  the  muscles  of  the  neck  may  reveal  some  tenderness  and  stiffness, 
which  is  increased  by  manipulation.  Pain  in  the  back  and  legs  is  a 
common  complaint,  but  the  significance  of  this  symptom  is  equivocal. 
In  our  experience  lumbar  puncture  on  the  second  day,  when  we  were 
so  fortunate  as  to  have  an  opportunity  of  performing  it,  yielded  a 
purulent  fluid  at  high  pressure.  With  the  third  day  all  the  symptoms 
shew  marked  aggravation.  Dehrium  becomes  more  marked,  and  may 
be  accompanied  by  violence  rather  than  restlessness.  The  delirium 
may  be  of  a  very  noisy  character,  the  patient  disturbing  the  whole 
ward  with  his  shouts  and  cries.  Towards  the  end  of  the  third  day 
dehrium  may  merge  somewhat  abruptly  into  coma  with  complete 
inabihty  to  swallow.  Head  retraction  becomes  more  marked,  retention 
of  urine,  if  it  has  not  occurred  before,  is  now  complete.  The  aspect  of 
the  patient  at  this  stage  may  appear  wellnigh  desperate.  He  lies  pro- 
foundly comatose,  his  head  retracted  between  his  shoulders,  mucus 
ratthng  in  his  throat,  the  respiration  hurried  and  irregular  in  rhythm, 
and  swallowing  an  impossibility.  And  yet  this  perilous  state,  which 
would  appear  to  signify  a  condition  of  profound  toxaemia,  is  in  fact 
largely  the  expression  of  increased  cerebro-spinal  pressure.  If  the  theca 
is  tapped  and  exit  given  to  the  excess  of  fluid  early  and  frequently 
enough,  such  an  apparently  hopeless  case  may  be  led  to  a  complete 
and  early  recovery.  The  cerebro-spinal  fluid  in  these  cases  is  at  very 
high  pressure,  from  two  to  three  oimces  being  easily  run  off  before  the 
fluid  assumes  its  normal  rate  of  flow.  The  fluid  is  purulent  and  may 
contain  flakes  or  clots  of  pus.  On  the  fourth  day  herpes  begins  to  make 
its  appearance,  usually  on  the  lips  or  heUces  of  the  ears.  This  eruption 
occurred  on  about  one-third  of  our  cases.  At  about  the  same  date 
a  macular  reddish  purple  rash  appears  on  the  abdomen,  the  thighs, 
extensor  surfaces  of  the  forearms  and  legs,  the  backs  of  the  hands 
and  dorsal  surfaces  of  the  feet.  The  older  physicians  regarded  the 
appearance  of  this  rash,  in  distinction  to  the  petechial  form,  as  a 
favourable  prognostic.  Our  own  experience  leads  to  the  conclusion 
that  a  rash  appearing  on  the  fourth  or  fifth  day  occurs  in  cases  which 
either  recover  or  lapse  into  a  chronic  hydrocephahc  condition,  but 
in  which  the  disease  is  not  immediately  fatal.  The  course  towards 
recovery  of  these  profoundly  comatose   cases  is  in  some'  instances 


iv]  Acute  Forms  49 

almost  as  rapid  as  the  onset  of  coma  is  sudden.  The  profound  coma 
may  continue  for  about  two  days,  at  the  end  of  that  time  the  patient 
begins  to  swallow,  the  sphincters  resume  their  functions,  and  a  glimmer 
of  consciousness  is  discernible.  If  lumbar  puncture  is  persevered  in, 
recovery  may  be  very  rapid  and  \\ithout  relapse  or  sequela. 

On  the  other  hand,  although  consciousness  may  return,  headache 
and  intermittent  fever  may  continue  for  weeks  before  complete  recovery 
takes  place,  that  is  to  say,  the  disease  passes  into  a  sub-acute  stage. 
A  rapid  exacerbation  of  symptoms  on  the  third  or  fourth  day  is 
in  these  cases  by  no  means  the  rule.  In  many  delirium  does  not 
pass  into  coma,  though  the  fever  remains  high,  the  headache  is  intense, 
and  retraction  marked ;  the  patient  can  swallow  and  retention  of  urine 
passes  off.  With  regular  drainage  the  acute  symptoms  disappear  in 
a  week  or  ten  days,  though  irregular  attacks  of  fever,  with  increased 
headache  and  sometimes  vomiting,  may  occur  from  time  to  time  for 
weeks.  These  slight  relapses  are  usually  cut  short  by  lumbar  puncture. 
Should  this  fail,  the  intrathecal  injection  either  of  the  patient's  own 
serum,  or  of  an  antimeningococcal  serum,  may  cut  short  these  exacer- 
bations. A  practical  point  of  some  importance  is  the  variation  in  the 
amount  of  head  retraction  as  recovery  progresses.  This  symptom  may 
entirely  disappear  and  then  after  an  interval  again  become  marked. 
In  our  experience,  if  the  theca  is  tapped  under  these  conditions,  not 
only  does  the  fluid  run  at  considerable  pressure,  but  retraction  ceases. 
This  symptom  is  a  definite  index  of  raised  cerebro-spinal  pressure, 
and  a  clear  indication  for  interference. 

At  any  time  during  an  epidemic,  but  notably  towards  its  decline, 
a  certain  number  of  mild  or  abortive  cases  are  met  with.  Such  cases 
usually  begin  with  a  rigor,  accompanied  by  headache  and  followed 
by  vomiting.  There  is  often  retention  of  urine  for  a  day  or  so ;  head 
retraction  is  not  marked,  though  tenderness  and  stiffness  of  the  neck 
muscles  can  generally  be  discovered  on  careful  examination.  Delirium 
is  rarely  present,  a  rash  or  herpes  is  uncommon ;  Kernig's  sign,  however, 
is  always  present.  If  lumbar  puncture  is  performed,  it  yields  fluid  at 
considerable  pressure  containing  pus  cells.  Recovery  is  usually  rapid. 
Films  or  cultures  may  or  may  not  yield  the  meningococcus,  but 
seeing  that  infection  by  the  meningococcus  is,  as  far  as  our  present 
knowledge  goes,  the  only  non-fatal  form  of  purulent  meningitis,  it  is 
fair  to  assume  that  these  are  abortive  forms  of  the  disease.  That 
the  meningococcus  has  in  some  cases  been  recovered  from  the  throat 
though  not  from  the  cerebro-spinal  fluid,  adds  weight  to  this  supposition. 

F.  &  o  4 


CHAPTER   V 

SUB-ACUTE   AND   CHRONIC   CASES 

Four  tyjyes  of  case.  The  suppurative  type,  absence  of  excess  of 
cerebrospinal  ft.uid.  The  recrudescent  type,  irregular  crises. 
Relapsing  cases,  rarity  of  true  relapse.  Hydrocephalus  principal 
danger  in  chronic  cases,  adynamic  state.  Importance  of  repeated 
puncture.  Posterior  basic  meningitis,  identity  with  cerebrospinal 
fever. 

The  acute  cases  so  far  considered  run  a  course  in  wiiicli  the  patient 
either  dies  during  the  first  week,  or  is  on  the  way  towards  recovery 
within  about  a  fortnight.  In  a  considerable  number  of  cases,  however, 
after  slight  general  improvement,  fresh  symptoms  may  arise  which 
protract  the  course  of  the  disease  and  may  leave  the  ultimate  issue  long 
in  doubt.  The  diverse  types  of  cases,  which  tend  to  run  a  longer  and 
more  complex  course,  may  be  divided  into  the  following  groups : 

1.  Suppurative. 

2.  Recrudescent. 

3.  Relapsing. 

4.  Hydrocephalic. 

The  type  of  case,  to  which  it  is  proposed  to  apply  the  name 
suppurative,  is  characterized  by  the  fact  that  the  cerebro-spinal  fluid 
instead  of  becoming  clearer  becomes  thicker  and  more  purulent  day 
by  day.  The  onset  and  early  days  present  no  striking  difference  from 
the  ordinary  acute  cases.  The  subsequent  course,  however,  presents 
very  striking  points  of  difference,  which  are  illustrated  by  the  following 
cases.  A  patient  was  admitted  with  delirium  and  head  retraction. 
Lumbar  puncture  on  the  third  day  yielded  markedly  purulent  fluid. 
Considerable  relief  of  symptoms  followed  the  operation,  but  the 
succeeding  punctures,  instead  of  shewing  any  diminution  in  the  amount 
of  pus,  indicated  an  increase.  The  patient  died  on  the  twenty-second 
day  of  his  illness,  having  been  for  a  number  of  days  in  an  adynamic  state 
with  variations  between  complete  consciousness  and  hebetude.    Lumbar 


CH.  v]  Sub-acute  and  Chronic  Cases  51 

puncture  yielded  purulent  fluid  at  fair  pressure  and  in  considerable 
quantity  until  the  fifteenth  day,  when  only  one  drachm  could  be 
obtained.  Subsequent  punctures  never  yielded  more  than  one  or  two 
drachms.  Post-mortem  the  base  of  the  brain  and  spinal  cord  (Plate  X, 
fig.  2)  were  coated  with  thick  inspissated  pus ;  there  was  no  marked  excess 
of  fluid.  In  another  case,  lumbar  puncture  on  the  fourth  day  yielded 
markedly  purulent  fluid  in  fair  quantity  and  at  considerable  pressure. 
The  fluid  in  subsequent  specimens  shewed  an  increasing  quantity  of 
pus ;  on  the  sixth  day  large  clots  of  pus  blocked  the  cannula.  On  the 
ninth  day  only  half  an  ounce  of  purulent  fluid  could  be  obtained,  the 
amount  fell  to  two  drachms  on  the  fifteenth  day.  From  this  date  until 
death,  which  occurred  on  the  nineteenth  day,  only  one  or  two  drachms 
were  yielded  of  comparatively  clear  fluid  containing  little  pus.  Con- 
siderable relief  of  symptoms  followed  the  earlier  pimctures,  but  as  less  and 
less  fluid  could  be  drained  ofl^,  the  patient  sank  into  an  adynamic  state, 
in  which  he  died.  Post-mortem  the  base  of  the  brain  was  covered  with 
thick  pus  (Plate  VIII),  which  extended  down  the  cord  entirely  covering 
it.  The  pus  was  so  thick  and  adherent  that  it  could  not  possibly  have 
flowed  through  any  cannula.  There  was  no  excess  of  cerebro-spinal 
fluid.  The  absence  of  excess  of  fluid  in  these  cases,  coupled  with  the 
fact  that  none  could  be  obtained  by  lumbar  puncture,  affords  a  striking 
contrast  to  the  excess  which  was  found  in  all  other  post-mortems  in 
our  experience.  The  phenomena  observed  in  these  cases  would  indicate 
that  there  exists  a  type  of  case  in  which  the  salient  feature  is  that  the 
infection  of  the  meninges  manifests  itself  in  the  secretion  of  dense 
adherent  pus.  The  earlier  stages  of  the  invasion  are  accompanied  by 
the  usual  out-pouring  of  an  excess  of  cerebro-spinal  fluid,  but  as  the 
secretion  of  pus  becomes  estabhshed,  excess  of  cerebro-spinal  fluid 
disappears.  These  cases  do  not  die  with  signs  of  increased  cerebro- 
spinal pressure,  but  sink  into  an  adynamic  state  clinically  bearing  some 
likeness  to  that  seen  in  obstructive  suppression  of  urine.  It  would 
appear  as  though  the  entire  secretory  mechanism  of  the  cerebro-spinal 
fluid  were  paralysed  by  the  pyogenic  process.  A  striking  feature  of 
these  cases  is  that  neither  constant  lumbar  puncture,  nor  the  intrathecal 
injection  of  anti-meningococcal  serum,  prevented  either  the  secretion  of 
increasingly  dense  pus  or  the  steady  progress  of  the  disease. 

In  discussing  the  gradual  recovery  of  acute  cases,  attention  was 
called  to  the  fact  that  progress  was  often  not  a  uniform  advance,  but 
was  marked  by  crises,  accompanied  by  cerebral  symptoms,  interrupting 
the  apyrexial  course  of  convalescence.     In  some  cases,  when  the  acute 

4—2 


52  Sub-acute  and  Chronic  Cases  [CH. 

symptoms  have  subsided,  the  temperature  remains  raised  for  a  period 
of  possibly  some  weeks.  The  course  of  the  fever  is  attended  by  marked 
remissions.  These  may  be  of  so  regular  a  character  as  to  simulate 
a  tertian  ague.  By  the  older  writers  stress  is  laid  on  the  difficulties 
which  attend  the  diagnosis  of  cerebro-spinal  fever  from  pernicious 
malaria.  Accompanying  this  fever  there  is  usually  some  headache  and 
a  certain  amount  of  mental  hebetude.  Chart  4  in  Chapter  II  well 
illustrates  this  type  of  fever.  In  this  instance  lumbar  puncture  was 
performed  in  the  early  stages,  but  subsequently  discontinued;  the 
patient  made  a  good  recovery.  This  persistent  temperature  would 
appear  to  indicate  that  the  infective  process  in  the  meninges  is  still 
active.  Support  is  given  to  this  view  by  the  fact  that,  in  other  cases 
with  persistent  temperature,  lumbar  puncture  repeated  daily  for  a  few 
days  brought  the  temperature  permanently  down  to  normal,  and  a 
rapid  convalescence  ensued.  In  other  cases  again  the  temperature  may 
remain  normal  for  a  few  days,  and  then  a  rise  of  temperature  occurs 
accompanied  by  headache,  vomiting  and  perhaps  retraction  of  the 
neck.  If  lumbar  puncture  is  performed,  a  fair  quantity  of  fluid  flows 
at  considerable  pressure,  this  fluid  is  clear  and  contains  few  cellular 
elements;  the  meningococcus  can  however  often  be  cultivated,  though 
with  difficulty,  its  appearance  and  disappearance  often  coinciding  with 
the  variations  in  the  clinical  condition.  The  accompanying  chart 
(Chart  5)  shews  these  variations  breaking  in  upon  the  steady  progress 
of  convalescence.  These  slight  crises  are  obviously  due  to  a  rise  in 
cerebro-spinal  pressure,  and  may  be  regarded  as  evidence  of  a  renewal 
of  bacterial  activity.  The  practical  point  is  that,  when  such  crises 
arise,  they  form  a  definite  indication  for  lumbar  puncture.  In  our 
experience,  not  only  was  an  increase  of  cerebro-spinal  pressure  always 
found,  but  the  relief  of  this  condition  secured  either  a  period  of  freedom 
from  fever  and  cerebral  symptoms  or  permanent  cure.  Had  drainage 
not  been  maintained,  it  is  probable  that  a  prolonged  period  of  irregular 
fever,  such  as  has  been  before  alluded  to,  would  have  ensued.  In  some 
instances,  in  spite  of  drainage  by  lumbar  puncture,  these  crises  recur. 
In  one  case  under  our  care  the  intrathecal  injection  of  5  c.c.  of  the 
patient's  own  serum  entirely  cut  short  fever  and  cerebral  symptoms, 
and  was  followed  by  convalescence.  In  our  experience  these  apyrexial 
periods  have  not  exceeded  six  or  seven  days.  Sophian  records  a  period 
of  ten  days.  The  important  point  is  that  Kernig's  sign  is  present 
throughout,  and  thus  distinguishes  a  late  recrudescence  from  a  true 
relapse. 


V] 


Sub-acute  and  Chronic  Cases 


53 


Authorities  differ  markedly  as  to  the  frequency  of  relapse  in  this 
disease.  The  fundamental  cause  of  this  discrepancy  is  the  varying 
significance  attached  by  different  observers  to  the  term  relapse.  Ker 
records  relapses  in  15-20  per  cent,  of  his  cases.  Sophian,  on  the  other 
hand,  has  met  with  a  true  relapse  in  under  5  per  cent,  of  his  cases  only. 
This  author  further  suggests  that  cases  regarded  as  relapses  may  have 
been  all  along  slightly  hydrocephalic.  A  case  under  our  own  care 
strengthens  this  assumption..  A  man  who  had  passed  through  a  com- 
paratively mild  attack  had  been  free  from  symptoms  for  ten  days; 
Kernig's  sign  was  however  still  present.  He  was  allowed  to  get  up. 
The  next  day  he  was  seized  with  headache  and  vomiting ;  a  considerable 
quantity   of   cerebro-spinal    fluid    was   withdrawn    at   high   pressure. 

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Symptoms  of  hydrocephalus  rapidly  developed,  the  amount  of  fluid 
obtained  from  lumbar  puncture  gradually  diminished,  and  he  died  with 
all  the  signs  of  cerebral  compression  four  weeks  afterwards.  Post- 
mortem the  third  and  fourth  ventricles  were  found  dilated.  The  upper 
dorsal  region  of  the  cord  was  covered  with  thick  pus  and  adherent  to 
the  theca.  On  holding  up  the  cord  with  the  theca  intact,  bulging  of 
fluid  was  obvious  as  far  as  the  level  at  which  this  coating  was  present ; 
the  theca  was  flaccid  below.  It  is  reasonable  to  suppose  that  in  this 
case  interference  with  the  circulation  of  fluid  had  occurred  owing  to 
adhesions  following  upon  the  original  purulent  exudate.  The  increased 
movement  involved  in  walking  may  have  upset  the  balance  of  the 
circulation  to  such  an  extent  as  to  lead  to  hydrocephalus.  The  patho- 
logical  conditions  found,  coupled  with  the  presence  of  Kernig's  sign 


54  Sub-acute  and  Chronic  Cases  [ch. 

throughout,  suggest  that  this  case  should  be  recorded  as  a  recrudescence 
rather  than  a  true  relapse.  As  has  been  shewn  in  discussing  recrudescence, 
fever  and  symptoms  may  be  absent  for  as  long  as  ten  days,  and  yet 
the  meningococcus  be  recovered  in  the  cerebro-spinal  fluid  at  the  end 
of  that  time.  Kernig's  sign  is  as  a  rule  a  reliable  guide  as  to  the 
persistence  of  infection  of  the  meninges.  In  one  of  our  cases,  which 
was  still  febrile,  it  was  unobtainable  for  a  few  days,  and  then  reappeared. 
The  absence  of  Kernig's  sign,  coupled  wiih  an  apyrexial  state  of  more 
than  ten  days  duration,  would  be  necessary  to  distinguish  a  genuine 
relapse  from  a  recrudescence.  That  genuine  relapses  occur  is  beyond 
question,  but  their  frequency  is  doubtful.  Lieutenant  Colonel  Adami 
informs  us  of  the  case  of  a  private  soldier  in  the  Canadian  contingent 
who  was  taken  ill  while  crossing  the  Atlantic.  When  recovered,  he  went 
on  furlough  to  his  friends  and  there  died  suddenly  from  the  after 
effects  of  cerebro-spinal  fever  long  weeks  after  the  primary  attack. 
The  possible  explanation  of  such  cases  will  be  referred  to  in  discussing 
hydrocephalus. 

In  the  preceding  chapters  it  has  been  shewn  that  death  may  take 
place  with  starthng  suddenness  at  the  very  onset,  or  the  course 
of  the  disease  may  be  uniformly  downwards  untilthe  fatal  event  is 
reached  at  the  end  of  the  first  five  days.  Where  diffuse  suppuration 
occurs,  the  case  may  be  prolonged  until  the  third  or  fourth  week. 
Beyond  this  date  death,  when  it  occurs,  is  due  to  one  cause  and  one 
cause  alone — the  development  of  hydrocephalus.  Cases  of  chronic 
meningitis  in  our  experience  are  not  only  similar  in  their  cUnical  features, 
but  the  anatomical  conditions  are  also  in  the  main  identical.  The 
development .  of  hydrocephalus  is  the  comphcation  most  to  be  feared 
after  the  first  week  of  illness.  Extreme  vigilance  is  needful  to  recognize 
the  earlier  symptoms,  as  a  guide  to  prompt  and  methodical  treatment. 

It  is  of  the  greatest  importance  to  recognize  at  what  an  early  stage 
dilatation  of  the  ventricles  can  take  place.  A  case  under  our  care 
died  suddenly  from  an  intercurrent  abdominal  haemorrhage  on  the 
tenth  day.  The  case  was  of  moderate  severity  and  appeared  to  be 
improving  at  the  time  of  death.  All  the  ventricles  of  the  brain  were 
found  markedly  dilated,  as  is  shewn  in  Plate  IX,  fig.  2  which  was 
drawn  at  the  post-mortem.  The  amount  of  pus  was  small  and  mostly 
situated  at  the  base  of  the  brain.  A  considerable  quantity  was 
however  present  in  the  region  of  the  cisterna  magna ;  and  the  cerebellum 
was  adherent  to  the  roof  of  the  fourth  ventricle.  It  is  doubtful  whether 
occlusion  can  become  complete  at  so  early  a  stage ;  in  the  case  described 


v]  Suh-acute  and  Chronic  Cases  56 

an  oimce  and  a  half  of  fluid  had  been  withdrawn  by  lumbar  puncture 
sixteen  hours  before  death.  So  large  an  amount  of  fluid  must  partly 
have  been  derived  from  the  ventricles  themselves. 

The  onset  of  hydrocephalus  is  insidious,  the  distinguishing  symptoms 
emerging  but  slowly  from  the  general  aspect  of  the  case.  At  the  latter 
part  of  the  first  week,  although  the  more  acute  symptoms  may  have 
abated  and  the  patient  is  not  in  obvious  danger,  the  headache  increases 
in  severity.  Dehrium  may  persist  and  is  usually  noisy  in  character, 
a  constant  complaint  of  headache  dominating  all  other  symptoms.  If 
the  theca  is  tapped  at  this  stage,  a  large  quantity  of  fluid  escapes  at 
very  high  pressure.  This  operation  aft'ords  marked  reUef  to  the 
symptoms,  the  patient  often  passing  straight  from  the  anaesthetic  into 
several  hours  of  C[met  slumber.  Generally  within  twenty-four  hours 
the  headache  returns  with  equal  severity,  and  lumbar  puncture  yields 
fluid  at  equally  high  pressure.  The  temperature  remains  at  a  moderate 
height,  100-101  with  irregular  remissions.  A  rigor  may  occur  at  this 
stage,  and  its  appearance  is  markedly  suggestive  of  the  presence  of 
hydrocephalus.  The  pulse  is  of  moderate  frequency  and  of  good  tension. 
Retention  of  urine  may  be  present,  but  as  a  rule  at  this  stage  the 
sphincters  are  unafl'ected.  These  symptoms  may  continue  with  slight 
daily  variations  through  the  second  week.  In  a  considerable  proportion 
of  cases  a  sudden  and  striking  change  makes  its  appearance  at  the 
latter  part  of  the  second  week.  This  change  may  be  ushered  in  by 
a  rigor,  in  itself  a  suggestive  symptom.  Following  the  rigor  or  without 
this  warning,  the  patient  lapses  comparatively  suddenly  into  an 
adynamic  state.  This  condition  is  characterized  by  profuse  sweating, 
a  feeble  running  pulse  and  incontinence  both  of  urine  and  faeces.  All 
complaints  of  headache  cease  and  low  muttering  delirium,  merging  into 
unconsciousness,  replaces  the  previous  monotonous  cries  of  suffering. 
The  significance  of  this  phase  and  its  prompt  recognition  are  of  supreme 
importance.  In  our  experience  this  crisis  has  always  heralded  a  long 
and  anxious  struggle,  which  in  fatal  cases  has  been  attended  by 
pathological  evidence  of  well-marked  hydrocephalus.  A  source  of  error 
to  be  avoided  lies  in  the  fact  that,  where  lumbar  puncture  has  been 
frequently  practised,  this  adynamic  condition  is  apt  to  be  attributed 
to  excessive  drainage  of  the  sub-arachnoid  space.  On  this  supposition 
the  wiser  course  may  appear  to  be  abstention  from  active  interference, 
and  a  recourse  to  purely  stimulating  measures.  As  a  matter  of  fact, 
the  truth  lies  far  otherwise;  if  lumbar  puncture  be  performed  at  this 
stage,  a  considerable  quantity  of  fluid  is  yielded  at  high  pressure.    The 


56  Sub-acute  and  Chronic  Cases  [ch. 

crisis  is  an  index,  not  of  exhaustion  but  of  pressure  affecting  the  medulla. 
Further,  the  relief  of  pressure  is  attended  with  improvement,  possibly 
slight,  but  always  obvious.  These  facts  warrant  a  perseverance  in 
repeated  lumbar  puncture.  In  spite  of  the  apparently  desperate 
condition  of  the  patient,  the  operation  has  in  our  hands  been  entirely 
free  from  danger.  The  subsequent  course  reproduces  the  classical 
picture  of  chronic  meningitis.  The  body  wastes  with  extreme  rapidity ; 
vomiting  occurs,  but  is  not  a  sufficiently  marked  symptom  to  account 
for  the  rapid  emaciation,  which  is  presumably  trophic  in  character. 
Carphology  and  subsultus  tendinum  are  marked  symptoms,  and  any 
movement  is  attended  by  tremors.  In  addition  to  head  retraction, 
rigidity  of  other  muscles  rapidly  makes  its  appearance.  The  elbows 
and  knees  become  increasingly  rigidly  flexed,  so  that  any  movement  is 
attended  with  considerable  pain.  The  mental  condition  is  one  of 
apathy,  varied  by  spells  of  quiet  muttering  delirium.  The  mask-like 
face  of  the  patient  reveals  no  consciousness  of  persons  and  events 
around  him,  though  the  sight  of  food  or  drink  sometimes  ehcits  a  gleam 
of  recognition.  In  this  connection  great  stress  must  be  laid  on  the 
importance  of  feeding  these  patients.  With  regard  to  food  they  behave 
very  much  like  some  forms  of  imbecile,  at  times  rolhng  their  food  in 
their  mouths  without  swallowing,  or  even  spitting  it  out.  It  may  thus 
appear  at  first  sight  that  they  are  unable  to  swallow ;  the  exercise  of 
patience  on  the  part  of  a  nurse,  to  whom  they  are  accustomed,  generally 
results  in  their  taking  a  full  meal.  The  condition  of  the  optic  discs 
was  repeatedly  observed  in  hydrocephalic  cases;  beyond  marked 
fullness  of  the  veins  there  were  no  pathological  changes.  In  cases 
which  recovered,  the  ophthalmoscopical  appearance  was  normal,  and 
vision  was  unimpaired.  Direct  evidence  of  hydrocephalus  may  some- 
times be  supplied  by  the  presence  of  MacEwen's  sign.  Sir  William 
MacEwen  has  called  attention  to  a  change  in  the  note  elicited  on  per- 
cussing the  skull  which  occurs  when  there  is  excess  of  fluid  within  the 
ventricles.  The  normal  note  yielded  on  percussion  of  the  skull  of  the 
adult  is  high-pitched,  in  technical  terms  a  pure  osteal  note.  When 
the  ventricles  are  distended,  percussion  about  the  pterion  yields  a 
note  of  a  more  resonant  quality.  A  further  point  is  that  the  area  of 
resonance  can  be  made  to  shift  by  altering  the  position  of  the  patient's 
head.  If  the  patient  hangs  his  head  to  one  side,  the  greatest  resonance 
is  over  the  lower  parietal  bone.  On  reversing  the  position  of  the  head, 
the  area  of  resonance  is  now  found  over  the  opposite  parietal.  This 
sign  is  more  easily  elicited  in  children  than  in  adults ;   its  presence  may 


v]  Sub-acute  and  Chronic  Cases  57 

give  confirmation  to  the  evidence  of  liydroceplialus  supplied  by  other 
symptoms.  In  some  cases  a  sudden  alteration  in  the  lumbar  puncture 
fluid  takes  place  which  is  of  very  grave  significance.  Lumbar  puncture 
yields  a  progressively  diminishing  amount  of  flmd.  Finally  a  point  is 
reached  when  only  a  drachm  or  two  of  perfectly  clear  fluid  can  be 
obtained.  Pimcture  as  high  as  the  last  dorsal  vertebra  yields  no  better 
result,  and  should  be  avoided,  as  in  our  experience  it  has  given  rise  to 
transient  though  alarming  reflex  phenomena.  In  fatal  cases  this  con- 
dition persists  until  the  end;  the  emaciation  becomes  extreme,  the 
pulse  feebler,  until  the  supervention  of  Cheyne-Stokes  breathing  or 
sudden  respiratory  failure  brings  about  the  fatal  issue.  Post-mortem 
a  complete  obstruction  in  the  sub-arachnoid  space  explains  the 
condition.  Another  not  imcommon  cause  of  death  is  the  invasion  of 
the  stagnant  cerebro-spinal  fluid  by  some  other  organism,  such  as  the 
pneumococcus.  "When,  however,  the  obstruction  is  not  complete,  and 
the  cerebro-spinal  fluid  stiU  flows  in  fair  quantity  on  puncturing  the 
theca,  improvement  is  slowly  manifested,  and  continues  till  complete 
recovery  is  reached.  The  consciousness  slowly  returns,  the  sphincters 
regain  their  tone,  rigidity  disappears,  and  the  patient  rapidly  gains 
flesh. 

Arguing  from  the  close  similarity  between  the  symptoms  of  fatal 
cases  and  some  who  recover,  it  may  fairly  be  assimied  that  the  latter 
were  cases  of  hydrocephalus  in  which  there  was  interference  with  the 
circulation  of  the  -cerebro-spinal  fluid,  stopping  short  of  complete 
occlusion.  It  may  also  reasonably  be  supposed  that  such  occlusion  may 
exist  in  a  minor  degree  without  causing  the  complete  chnical  picture 
of  hydrocephalus.  CHnically  this  c^uestion  can  be  answered  in  the 
affirmative.  A  definite  group  of  cases  present  the  early  symptoms 
without  reaching  the  extreme  degree.  After  the  subsidence  of  the  early 
acute  symptoms,  the  patients  complain  of  agonizing  and  continuous 
headache.  This  headache  is  at  once  removed  by  lumbar  pimcture, 
when  fluid  runs  in  large  quantity  at  high  pressure.  AVithin  twenty- 
four  hours  the  headache  may  be  as  bad  as  ever,  and  again  lumbar 
puncture  aSords  fresh  relief.  Such  a  condition  may  go  on  for  days, 
and  then  gradually  lessen.  In  some  cases  these  headaches  cease  abruptly, 
and  thenceforward  the  patient  is  entirely  free  from  pain.  Adopting 
the  reasonable  assumption  that  this  headache  is  an  indication  of 
increased  pressure  in  the  cerebro-spinal  fluid,  its  cessation  must  imply 
that  an  increase  in  pressure  suddenly  ceases  to  be  formed.  It  can 
hardly  be  supposed  that  this  is  due  to  a  sudden  diminution  of  secretory 


58  Sub-acute  and  Chronic  Cases  [ch. 

activity ;  the  conclusion  is  much  more  probable  that  the  normal  channels 
of  drainage  become  adequately  re-established.  Such  a  sudden  re- 
establishment  is  quite  conceivable,  for  persistent  puncture  may  gradually 
lessen  the  maximum  tension  below  a  certain  critical  point,  at  which  the 
normal  drainage  is  able  to  take  place.  Some  evidence  in  this  direction 
has  been  obtained,  as  a  progressive  diminution  in  the  amount  of  fluid 
withdrawn  has  preceded  the  clinical  crisis  of  sudden  loss  of  headache. 
As  all  such  cases  in  our  practice  were  drained  daily  if  necessary,  the 
question  as  to  whether  they  would  have  developed  well-marked 
hydrocephalus  cannot  be  answered.  When  recovery  takes  place,  it  is 
usually  complete.  In  our  experience  any  signs  of  mental  enfeeblement 
were  entirely  absent.  When  the  long  period  of  compression  and 
unconsciousness  is  considered,  such  complete  recovery  is  a  matter  for 
some  astonishment.  Physically  hydrocephalus  leaves  no  sequelae ;  the 
heart  is  miaffected  and  a  local  palsy  is  a  very  rare  event.  Stiffness 
and  pain  in  the  back  may  persist  for  a  long  time :  several  of  our  patients 
were  unable  to  march  with  a  pack  for  months.  Late  in  the  epidemic 
of  1915  a  case  was  brought  into  our  ward  suffering  from  hydrocephalus. ' 
There  was  a  history,  dating  back  some  weeks,  of  an  acute  attack  of 
fever  attended  with  headache  and  vomiting.  On  admission  there  was 
occasionally  a  day  or  two  of  severe  headache,  which  passed  off;  the 
temperature  was  normal,  the  cerebro-spinal  fluid  was  sterile.  Death 
took  place  somewhat  suddenly  from  respiratory  failure.  Post-mortem 
the  ventricles  were  found  dilated  with  sterile  fluid  and  there  were 
adhesions  about  the  roof  of  the  fourth  ventricle,  which  occluded  the 
foramen  of  Majendie.  The  supposition  may  be  hazarded  that  this 
condition  was  the  result  of  a  past  mild  attack  of  cerebro-spinal  fever. 
We  have  been  informed  by  Major  Burton  Fanning  of  a  case  very 
similar  to  this,  in  which  the  acute  attack  had  taken  place  some  three 
months  before.  The  patient  had  passed  through  an  attack  of  cerebro- 
spinal fever  in  France,  and  been  invalided  home.  While  on  leave  he 
had  begun  to  complain  of  headache  for  which  he  was  admitted  to  hospital, 
though  he  was  sufficiently  well  to  be  up  during  the  daytime.  Death 
took  place  during  sleep.  At  the  post-mortem  well  marked  hydro- 
cephalus was  found  involving  the  third  and  lateral  ventricles;  the  iter 
was  completely  blocked.  A  similar  condition  would  account  for  some 
of  the  so-called  relapsing  cases,  where  death  takes  place  at  some  con- 
siderable period  after  the  primary  attack,  from  which  the  patient  was 
supposed  to  be  either  convalescent  or  cured.  It  is  important  to  realize 
that  a  case  may  first  come  under  observation  when  definitely  suffering 


v]  Sub-acute  and  Chronic  Cases  59 

from  hydrocephalus,  the  preliminary  acute  attack  having  been  regarded 
as  influenza  or  a  mild  attack  of  pneumonia.  The  signs  of  hydro- 
cephalus may  not  be  nearly  so  severe  as  in  the  more  typical  cases 
described  above.  The  mental  quahties  may  be  merely  dulled,  and 
these  with  the  attendant  headache  may  shew  a  definite  alternation  of 
good  and  bad  days.  Such  an  alternation  of  symptoms  has  already  been 
referred  to  in  connection  with  fever,  but  in  these  cases  the  variations 
may  occur  without  any  rise  of  temperature. 

Gee  and  Barlow  in  1878  published  a  paper  in  the  St  Bartholomew's 
Hospital  Reports  entitled,  "On  Cervical  Opisthotonos  in  Infants."  In 
this,  attention  was  called  to  a  previously  undescribed  condition,  occurring 
in  infants,  characterized  by  initial  fever  with  vomiting,  and  followed  on 
the  third  or  fourth  day  by  retraction  of  the  head.  A  large  proportion 
of  the  cases  ran  a  chronic  course,  characterized  by  head  retraction, 
opisthotonos,  tonic  spasms  of  the  hmbs  and  wasting.  Accumulated 
pathological  evidence  shewed  that  these  symptoms  were  always 
associated  with  either  purulent  meningitis  about  the  base  of  the  brain, 
or  inflammatory  thickening  in  the  region  of  the  cerebellum  and  medulla, 
notably  near  the  cisterna  magna.  That  is  a  posterior  basic  meningitis. 
The  chronic  form  of  the  disease  was  found  to  be  marked  by  hydrocephalus, 
due  apparently  to  the  occlusion  of  the  foramen  of  Majendie  and  the  fora- 
mina of  Luschka.  Carr  in  1897  suggested  the  possibiKty  that  compression 
by  inflammatory  exudation  might  cause  thrombosis  of  the  venae  Galeni, 
and  thus  produce  a  passive  hyperaemia  of  the  choroid  plexuses.  All 
the  earher  cases  observed  were  of  a  sporadic  character.  In  1898  Still 
isolated  a  diplo-coccus  from  the  cerebro-spinal  fluid  identical  in  its 
main  features  with  the  meningococcus  of  Weichselbaum.  Subsequent 
researches  have  estabHshed  the  id-entity  of  the  causative  organism  of 
posterior  basic  meningitis  with  Weichselbaum's  meningococcus.  The 
disease  has  occasionally  occurred  in  small  epidemics,  and  has  shewn  a 
seasonal  prevalence  identical  with  that  of  cerebro-spinal  fever.  Posterior 
basic  meningitis  may  be  regarded  as  cerebro-spinal  fever  with  certain 
clinical  differences  due  to  the  anatomical  development  of  childhood. 
Our  own  experience  of  cerebro-spinal  fever  having  been  almost  entirely 
acquired  amongst  soldiers,  we  do  not  lay  claim  to  experience  other  than 
that  of  ordinary  physicians  in  discussing  this  disease.  The  disease  usually 
occurs  in  children  from  six  months  to  two  years  of  age,  though  older 
children  may  be  affected.  The  onset  is  sudden,  often  accompanied  by 
a  convulsion,  generally  by  vomiting,  and  followed  by  a  rapid  rise  of 
temperature.     Persistent  screaming  may  be  a  marked  symptom  at  the 


60  Suh-acute  and  Chronic  Cases  [ch. 

onset.  Head  retraction  occurs  early,  appearing  on  the  first  day  in  half 
Lees  and  Barlow's  cases.  A  certain  number  of  those  attacked  die  in 
the  early  stage,  more,  probably,  than  are  recognized,  owing  to  death  , 
being  attributed  to  convulsions.  In  other  cases  head  retraction 
increases,  and  tonic  spasm  of  other  muscles  rapidly  follows,  the  arms 
and  legs  are  rigidly  flexed  and  opisthotoiaos  develops.  The  position  of 
the  limbs  varies  in  different  cases,  the  commonest  is  rigid  flexion  of 
both  arms  and  legs,  though  in  some  cases  there  may  be  rigid  extension 
of  all  four  limbs.  Vomiting  as  a  symptom  rarely  disappears  entirely, 
and  may  be  distressing.  The  respiration  is  generally  irregular  and  is 
frequently  of  the  Biot  or  cerebral  type,  with  irregular  periods  of  apnoea 
and  marked  sighing.  The  unmistakeable  hydrocephalic  cry  is  often 
present  at  this  stage,  and  rapid  wasting  accompanies  these  symptoms. 
Kernig's  sign  is  a  physiological  attribute  up  to  the  age  of  two  years, 
consequently  its  presence  is  of  no  clinical  value.  The  patency  of  the 
fontanelles  also  prevents  the  full  development  of  MacEwen's  sign. 
On  the  other  hand,  the  marked  bulging  which  is  always  present  supphes 
even  more  convincing  evidence  of  the  presence  of  hydrocephalus. 
The  chnical  picture  in  many  respects  closely  resembles  the  hydro- 
cephalic type,  as  seen  in  adults.  The  anatomical  condition  of  the 
infant's  bony  system,  however,  introduces  a  factor  which  essentially 
modifies  the  clinical  aspect  of  the  disease.  Owing  to  the  yielding 
nature  of  the  cranial  bones  and  the  patency  of  the  fontanelles,  increased 
cerebral  pressure  does  not  exercise  all  its  force  upon  the  nervous  elements, 
but  in  addition  produces  an  outward  thrust  upon  the  skull  cap  itself. 
The  results  of  this  centrifugal  pressure  are  twofold.  In  the  first  place, 
the  nervous  structures  are  to  some  extent  spared,  and  the  case  tends 
to  run  a  more  chronic  course  than  that  seen  in  the  adult.  In  the  second 
place,  the  parietal  bones  are  splayed  outwards  and  the  fontanelles 
bulge.  Pressure  on  the  orbital  plate  tends  to  turn  the  eyes  downwards, 
until  finally  the  classical  appearance  of  external  hydrocephalus  is  com- 
plete. Further,  the  slower  compression,  to  which  the  nervous  elements 
are  exposed,  gives  rise  to  the  occurrence  of  symptoms  which  are  but  rarely 
observed  in  the  more  rapid  course  of  the  disease  in  the  adult.  Of  these 
the  most  notable  is  the  common  occurrence  of  bhndness,  as  compared 
with  its  rarity  in  older  subjects.  Amaurosis  would  appear  to  be  of 
central  origin,  since  optic  neuritis  with  atrophy  is  extremely  rare. 
The  optic  lobes,  situated  as  they  are  immediately  beneath  the  already 
ossified  occipital  bone,  are  necessarily  exposed  to  greater  pressure  than  the 
motor  areas.     Pressure  thus  exerted  may  be  the  cause  of  the  bhndness. 


v]  Sub-acute  and  Chronic  Cases  61 

the  common  occurrence  of  occipital  tenderness  tends  to  strengthen 
this  supposition.  Deafness  by  contrast  is  less  common  in  posterior 
basic  meningitis  than  in  the  epidemic  form.  A  further  result  of  the 
prolonged  compression  of  the  brain  is  the  relative  frequency  of  subse- 
quent mental  impairment  compared  to  its  rarity  as  a  sequel  of  cerebro- 
spinal fever.  The  chronic  character  of  the  disease  is  shewn  by  Lees 
and  Barlow's  statistics,  which  give  an  average  duration  of  7-8  weeks 
for  30  cases.  Individual  cases  may  run  an  even  longer  course,  some 
lasting  as  long  as  nine  months.  The  mortality  is  very  high,  probably 
about  80  per  cent.  Death  usually  occurs  from  exhaustion.  Here,  as 
in  all  wasting  diseases,  the  body  is  peculiarly  liable  to  a  terminal 
bacterial  infection,  which  rapidly  becomes  generalized.  The  stagnant 
cerebro-spinal  fluid  affords  a  peculiarly  favourable  nidus  for  such  an 
invasion.  Infection  of  the  cerebro-spinal  fluid  at  this  stage  is  rapidly 
fatal.  The  infective  agents  are  generally  the  pneumococcus  or  the 
bacillus  coli. 

With  regard  to  treatment,  various  surgical  procedures  have  been 
devised  for  securing  drainage  of  the  cerebro-spinal  fluid.  Tapping  the 
ventricles,  trephining  the  occipital  bone,  and  various  other  methods 
of  drainage  have  all  been  practised.  No  method  has  hitherto  met 
with  sufficiently  marked  success  to  secure  its  general  adoption.  The 
diverse  possible  situations  of  the  seat  of  obstruction  may  render  an 
operation  planned  for  a  special  contingency  only  partially  successful  in 
securing  drainage.  As  in  all  cases  of  cerebro-spinal  fever,  the  patient 
so  often  comes  under  observation  too  late ;  the  obstruction  to  free 
circulation  of  fluid  is  already  formed.  Should  the  disease  be  met  with 
sufficiently  early,  treatment  by  daily  lumbar  puncture  would  hold  out 
considerable  hope  of  success. 


CHAPTER  VI 

COURSE   AND   PROGNOSIS 

Incubation.  Course.  First  day,  second  day,  stage  of  baffling 
symptoms,  third  day,  death  befwe  sixth  day  in  acute  fatal  type,  course 
of  recovery,  termination  by  crisis  and  lysis,  chronic  intermittent 
cases.  Immediate  prognosis  based  on  signs  and  symptoms,  date 
of  treatment,  age  of  patient,  stage  of  epidemic.  Remote  prognosis. 
Contrast  of  sequelae  in  earlier  and  later  epidemics. 

The  period  of  incubation  in  cerebro-spinal  fever  has  not  so  far  been 
determined  with  certainty,  and  rests  mainly  on  indirect  evidence.  As 
case  to  case  infection  is  very  difficult  of  identification,  evidence  derived 
from  this  source  is  only  occasionally  available.  In  our  experience  the 
facts,  which  throw  most  light  on  the  probable  period  of  incubation,  are 
derived  from  instances  in  which  a  case  occurred  amongst  troops,  hitherto 
free,  in  the  person  of  a  man  just  returned  from  leave.  Three  of  our 
cases  occurred  in  men  returned  from  leave,  and  were  the  first  instances 
of  the  disease  met  with  in  their  station.  In  one  case  at  Bishop's 
Stortford,  a  man  returned  from  four  days'  leave  and  developed  the 
disease  on  the  day  of  his  return.  At  Houghton  Regis  again  a  man 
returned  from  four  days'  leave  and  developed  the  disease  in  a  fulminating 
form  the  day  after  his  return.  In  another  case  occurring  at  Watford, 
the  disease  developed  the  day  after  the  man's  return  from  five  days' 
leave  spent  in  London,  where  cerebro-spinal  fever  was  then  prevalent. 
These  three  cases  were  the  first  to  occur  in  their  respective  stations, 
and  it  may  be  assumed  that  the  disease  was  contracted  while  the  man 
was  on  leave.  On  this  assumption  the  period  of  incubation  cannot,  at 
the  longest,  have  been  more  than  four  days  in  one  case,  and  five  days 
in  the  other  two.  Two  other  cases  developed  the  disease  on  return 
from  leave,  the  actual  onset  occurring  only  three  days  after  the 
commencement  of  leave.  As  other  cases  had,  however,  occurred 
previously  in  the  station,  the  evidence  is  thus  less  definite  than  in 
the  former  cases.  The  evidence  furnished  by  these  five  cases  would 
put  the  period  of  incubation  at  from   three  to  five  days.     Turning 


CH.  vi]  Course  and  Prognosis  63 

to  the  case  of  men  who  contracted  the  disease  while  on  leave,  two  cases 
occurred  at  Littleport  in  men  who  were  on  leave  for  three  and  four  days 
from  FeUxstowe  and  Bury  respectively.  The  first  of  these  two  men 
to  fall  ill  came  from  Bury,  where  the  disease  was  not  then  prevalent, 
the  first  symptoms  appearing  on  the  third  day  of  his  leave. 
The  second  man  came  from  Fehxstowe,  where  epidemic  meningitis 
had  plready  appeared  among  the  troops ;  the  evidence  derived  from 
his  case  is  therefore  equivocal.  In  the  case  of  the  first  man,  it  may  be 
remarked  that  he  came  from  a  station  which  was  free  from  meningitis 
throughout  the  winter  and  spring,  and  that  meningitis  had  already 
appeared  in  the  neighbourhood  of  Littleport.  A  consideration  of  these 
facts  warrants  the  assumption  that  this  man  contracted  the  disease  at 
Littleport,  in  which  case  the  period  of  incubation  would  be  at  the  longest 
three  days.  In  another  instance,  a  man  developed  the  disease  fourteen 
days  after  going  on  leave,  but  as  furlough  was  granted  in  order  that 
he  might  visit  a  sick  sister,  it  is  possible  that  she  may  have  been  suffering 
from  an  unrecognized  form  of  cerebro-spinal  fever.  This  man  moreover 
came  from  Bury,  where,  as  has  been  stated  above,  the  disease  was  not 
prevalent,  into  a  district  where  it  had  already  appeared.  The  evidence 
regarding  the  length  of  incubation  in  this  case,  therefore,  runs  counter 
to  the  assumption  that  the  incubation  period  was  as  long  as  fourteen 
days.  Such  evidence  as  our  cases  are  capable  of  affording  would  lead 
to  the  conclusion  that  the  period  of  incubation  has  a  maximum  Hmit  of 
not  more  than  five  days.  Evidence  from  other  sources  is  furnished  by 
a  singularly  apposite  quotation  of  Netter's  from  Richter.  Regina  B. 
passed  the  entire  day  of  October  the  17th  with  a  family  where  there 
were  two  children  suffering  from  meningitis.  She  returned  to  her 
uncle's  house,  where  she  first  shewed  symptoms  of  cerebro-spinal  fever 
on  the  21st  of  October.  On  the  8th  of  November,  when  fully  con- 
valescent, she  received  the  visit  of  a  young  man,  who  in  his  turn 
developed  the  disease  on  the  10th  of  November.  This  young  man  had 
a  mild  attack,  and  was  able  to  return  to  his  office  on  the  15th  of 
November.  On  the  19th  of  November  his  neighbour  at  the  same 
desk  developed  the  disease.  This  remarkable  chain  of  infection  would 
point  to  an  incubation  period  of  from  two  to  four  days.  Sophian  quotes 
two  cases  which  are  sufficiently  unequivocal  to  have  a  distinct  bearing 
on  the  question.  In  the  year  1911  cerebro-spinal  fever  was  not  epidemic 
in  New  York.  There  was,  however,  at  that  date  an  extensive  epidemic 
in  Greece,  and  Greek  immigrants,  some  of  whom  were  suffering  from 
'the  disease,  were  arriving  in  the  Port  of  New  York.     A  doctor,  who 


64  Course  and  Prognosis  [ch. 

as  far  as  was  known  had  not  been  exposed  to  infection  from  meningitis, 
performed  a  post-mortem  examination  on  a  case  which  had  actually 
died  on  the  steamer.  At  the  end  of  24  hours  he  developed  a  mahgnant 
form  of  the  disease.  The  second  case  was  that  of  another  doctor  who 
treated  a  Greek  immigrant  for  a  febrile  condition  other  than  meningitis ; 
five  days  afterwards  he  developed  the  disease.  Swabs  taken  from  the 
throat  of  the  patient  proved  him  to  be  a  carrier.  A  consideration  of 
the  evidence,  furnished  by  the  cases  which  have  been  set  forth,  tends 
to  shew  that  the  period  of  incubation  varies  between  three  and  five 
days.  The  former  Hmit  would  appear  to  be  the  more  usual  period, 
while  in  the  malignant  forms  this  may  be  still  further  shortened. 

The  course  of  epidemic  meningitis  has  already  been  to  some  extent 
sketched  in  deahng  with  the  various  phases  of  the  disease.  Certain 
features,  which  attend  the  progress  of  the  disease,  may  be  considered 
from  a  more  general  standpoint.  The  onset  is  as  a  rule  sudden,  and 
in  the  majority  of  cases  is  marked  even  more  definitely  by  a  rigor. 
Following  the  rigor,  the  first  day  is  accompanied  by  the  onset  of  fever 
and  the  rapid  development  of  the  earher  cerebral  symptoms,  headache 
and  vomiting.  The  course  of  the  second  day  is  frequently  marked  not 
only  by  no  aggravation  of  symptoms,  but  even  by  a  partial  improvement 
in  the  general  condition  of  the  patient.  This  apparent  pause  in  the 
march  of  the  disease  has  been  described  by  Netter  as  the  "periode  des 
symptomes  frustes,"  "the  stage  of  baffling  symptoms."  The  recogni- 
tion of  this  period  of  seeming  improvement  is  a  matter  of  great  practical 
importance.  A  considerable  number  of  cases  are  never  seen  on  the 
first  day,  and  the  apparent  improvement  on  the  second  may  either 
induce  a  sense  of  false  security,  or  appear  to  warrant  an  expectant 
attitude.  As  a  consequence,  time  may  be  allowed  to  go  by  without 
either  a  definite  diagnosis  being  arrived  at,  or  appropriate  treatment 
begun.  A  careful  and  judicious  examination  at  this  stage  will  probably 
discover  the  presence  of  Kernig's  sign,  and  some  stifliness  and  tenderness 
of  the  muscles  of  the  neck,  thiis  revealing  the  true  nature  of  the  malady 
masked  by  the  apparent  improvement.  The  presence  of  these  signs 
would  justify  lumbar  puncture.  The  character  of  the  fluid  yielded  by 
this  operation,  and  the  pressure  at  which  it  flows,  would  probably 
confirm  any  suspicion  which  may  have  been  entertained  as  to  the 
nature  of  the  case. 

When  the  experience  of  all  those  who  have  been  concerned  with 
the  treatment  of  the  disease  in  the  latter  epidemics  is  reviewed,  a 
remarkable  unanimity  of  opinion  is  found  to  exist  as  to  the  paramount 


vi]  Course  and  Prognosis  65 

importance  of  early  treatment.  Flexner's  statistics  furnish  a  striking 
proof  of  the  marked  value  of  treatment  begun  at  the  earliest  possible 
moment.  In  our  own  experience,  whenever  we  were  so  fortunate  as 
to  have  the  opportunity  of  beginning  treatment  at  an  early  stage,  the 
difference  in  results  was  very  striking  when  compared  with  those  obtained 
by  interference  at  a  later  period.  The  importance  of  the  recognition  of 
the  false  improvement  on  the  second  day  hes  not  only  in  the  intrinsic 
value  of  early  diagnosis  and  treatment,  but  also  in  that  this  apparent 
calm  is  the  herald  of  a  fresh  exacerbation.  With  the  third  day,  in 
spite  of  any  apparent  previous  improvement,  all  the  existing  symptoms 
are  aggravated,  and  fresh  ones  now  make  their  appearance.  Dehrium 
accompanies  the  existing  headache,  and  in  turn  may  rapidly  give 
place  to  coma.  Eetraction  of  the  head  and  muscular  rigidity  in  other 
parts  mark  the  more  remote  effects  of  increased  intra-cranial  pressure. 
By  this  time,  therefore,  the  classical  symptoms  of  the  disease  have 
become  manifest,  and  the  diagnosis  placed  beyond  doubt,  often, 
however,  after  the  unrecoverable  chance  of  early  treatment  has  been 
let  shp.  From  the  third  day,  in  fatal  cases,  the  symptoms  steadily 
and  rapidly  increase  in  gravity  until  death. 

In  commenting  on  the  cases  which  have  been  grouped  together 
under  the  name  acute  fatal  type,  attention  was  called  to  the  one  feature 
common  to  all,  that  they  shewed  no  response  whatever  to  treatment, 
their  course  being  uniformly  downwards.  As  a  measure  of  the  relentless 
march  of  the  disease  in  cases  of  this  nature,  it  may  be  noted  that  death 
practically  always  occurs  within  the  first  five  days.  Of  fourteen  deaths 
which  occurred  in  the  cases  under  our  care,  no  less  than  nine  occurred 
during  the  first  five  days  of  the  illness ;  in  contrast,  the  next  shortest 
period  in  which  death  occurred  was  on  the  nineteenth  day.  After 
a  long  interval,  in  which  no  cases  occurred  in  the  district  under 
our  charge,  an  acute  case  came  under  our  notice  in  December,  1915, 
which  again  illustrated  the  two  facts  just  insisted  upon,  an  illusory 
improvement  on  the  second  day,  and  a  fatal  termination  before 
the  end  of  the  fifth  day.  It  would  appear  as  though  the  acute  fatal 
type  was  more  than  a  mere  aspect  of  the  disease,  but  rather  represented 
the  power  of  endurance  of  the  body  in  cases  in  which  protective  reactions 
were  apparently  unable  to  develop.  In  this  connection  it  seems 
reasonable  to  suppose  that,  with  an  infection  of  such  virulence,  a  period 
of  about  five  days  marks  the  longest  time  in  which  the  primary  on- 
slaught of  the  disease  is  hkely  to  be  fatal.  Should  the  patient  survive 
the  fifth  day,  death,  if  it  occurs,  will  more  probably  be  brought  about 

F.  &G.  5 


66  Coiirse  and  Prognosis  [cH. 

by  some  other  condition  such  as  hydrocephalus  or  the  supervention  of 
diiiuse  suppuration.  In  cases  which  pass  the  fifth  day  and  then  recover, 
the  symptoms  may  persist  through  the  sixth  or  seventh  day  with 
apparently  unabated  severity.  More  usually,  however,  on  one  of  these 
days  or  at  the  longest  before  the  eighth  day  has  passed,  signs  of  improve- 
ment begin  to  manifest  themselves.  The  abatement  of  symptoms,  when 
once  begun,  may  be  very  rapid,  and  convalescence  is  soon  estabhshed. 
Such  a  sudden  improvement  may  be  accompanied  by  a  fall  of  temperature 
to  the  normal,  at  which  level  it  is  maintained.  Flexner  and  other 
authors  speak  of  this  sudden  and  permanent  ameHoration  of  symptoms 
as  termination  by  crisis,  and  contrast  its  features  with  the  more  gradual 
and  irregular  improvement  usually  observed,  which  they  call  termina- 
tion by  lysis.  This  sudden  fall  of  temperature  and  abatement  of 
symptoms  undoubtedly  bears  a  superficial  resemblance  to  the  true 
crisis,  as  seen  in  pneumonia  and  typhus.  It  may  be  doubted,  on  the 
other  hand,  whether  this  analogy  can  be  upheld,  since  an  almost  equally 
sudden  abatement  of  symptoms  may  be  observed  in  cases  of  chronic 
meningitis  from  the  twentieth  to  the  thirtieth  day.  Now  a  crisis  in 
the  strict  sense  of  the  term  involves  some  sudden  change  in  the  mutual 
relations  of  the  fluids  of  the  body  and  the  products  of  infection.  That 
such  an  essentially  vital  change  could  take  place  at  such  widely  different 
stages  of  any  disease  is  contrary  to  chnical  experience.  The  crisis  in 
pneumonia  may  take  place  on  the  fifth  day  and  that  of  typhus  on  the 
fourteenth,  but  the  crisis  of  each  disease  conforms  with  a  considerable 
degree  of  punctuahty  to  the  accustomed  course  of  one  or  other  disease. 
It  would  appear  more  probable  that  this  sudden  amelioration  is  due 
rather  to  the  opening  of  channels  of  drainage  from  the  sub-arachnoid 
space,  than  to  any  alteration  in  the  mutual  relations  of  the  fluids  of 
the  body.  Assuming  the  adequacy  of  such  an  explanation,  the  term 
crisis  would  appear  to  be  a  misnomer,  in  that  it  tends  to  suggest  a  vital 
process,  when  the  cHnical  symptoms  are  largely  to  be  explained  on 
physical  grounds.  When  the  dangers  present  up  to  the  fifth  day  have 
passed,  the  ultimate  outlook  is  by  no  means  certain.  Examination  of  the 
cerebro-spinal  fluid  may  shew  that,  instead  of  becoming  less  purulent, 
the  amount  of  pus  steadily  increases.  Such  a  condition  indicates  that 
the  case  is  passing  into  the  suppurative  stage,  in  which  the  course 
may  be  protracted  till  the  fourth  week,  but  almost  invariably  termin- 
ates fatally.  In  other  cases  excruciating  headache  may  persist  for 
many  days,  accompanied  by  great  tension  of  the  fluid  as  evidenced 
by    lumbar    puncture.      Under    such    coiaditions    hydrocephalus    may 


vi]  Course  and  Prognosis  67 

become  established  in  the  second  or  third  week,  its  onset  usually  being 
marked  by  a  sudden  lapse  into  an  adynamic  state.  Or  again  the  case 
may  run  a  long  course  with  irregular  attacks  of  fever,  accompanied 
by  headache.  Systematic  investigation  of  the  cerebro-spinal  fluid 
during  these  exacerbations  will  frequently  indicate  an  increase  of 
bacterial  activity  coinciding  with  each  aggravation  of  chnical  symptoms. 
In  chronic  cases  these  exacerbations  may  appear  in  a  remarkably 
regular  manner,  bad  days,  in  which  the  symptoms  are  severe,  alternating 
with  good  days  when  the  patient  appears  practically  convalescent. 
This  alternation  may  be  marked  by  a  corresponding  variation  in  tempera- 
ture, which  is  often  so  regular  as  to  simulate  a  tertian  ague  (Chart  4, 
p.  17).  Such  chronic  intermittent  cases  ultimately  make  a  good  re- 
covery, death  from  exhaustion,  except  in  hydrocephahc  cases,  being  a 
practically  unknown  event. 

The  variations  in  the  course  of  the  disease,  which  have  been  just 
described,  shew  that  prognosis  is  a  matter  of  considerable  difficulty. 
In  no  disease  commonly  seen  within  these  islands  can  such  dramatic 
changes  be  witnessed  as  in  the  diverse  phases  of  cerebro-spinal  fever. 
An  apparently  desperate  case  may  make  a  rapid  recovery,  while  one 
of  milder  onset  runs  a  uniformly  downward  course  terminating  in  death. 
Experience  is  rendered  even  more  fallacious  in  that  nothing  is  more 
bafiling  than  a  forecast  of  the  probable  results  of  treatment.  Such 
cHnical  guides  as  we  possess  may  be  considered  under  the  following 
heads:  1.  The  signs  and  symptoms  of  the  patient.  2.  The  date  at 
which  treatment  is  begun.  3.  The  age  of  the  patient.  4.  The  stage 
of  the  epidemic  at  which  the  patient  is  attacked. 

The  method  of  onset,  seen  in  fulminating  cases,  almost  always 
portends  a  fatal  result.  As  has  been  shewn  before,  sudden  loss  of 
consciousness  as  an  initial  symptom  is  not  necessarily  fatal.  This 
exception  is,  however,  so  rare  as  to  be  neghgible.  A  purpuric  rash 
appearing  in  the  first  24  hours  is  of  grave  prognostic  significance. 
A  petechial  rash  appearing  on  the  first  or  second  day  is  equally  un- 
favourable. The  presence  of  extreme  dyspnoea  in  a  marked  form  is 
in  our  experience  always  a  mortal  symptom.  Cyanosis  is  almost 
equally  unfavourable.  Of  physical  changes  restlessness  is  a  more 
unfavourable  prognostic  than  noisy  dehrium  or  profound  coma.  The 
supervention  of  hydrocephalus,  as  evidenced  by  a  sudden  lapse  into  an 
adynamic  state,  is  of  grave  but  not  fatal  significance.  High  fever  at 
the  onset,  an  irregular  pulse,  marked  retraction  and  carphology  have  not 
in  our  experience  betokened  a  necessarily  fatal  issue.     The  appearance 

5—2 


68  Cotirse  and  Prognosis  [ch. 

of  the  cerebro-spinal  fluid  at  the  onset  affords  no  criterion  of  the 
gravity  of  the  disease.  A  fluid  clear  at  one  puncture  may  be  intensely 
purulent  at  the  succeeding  one.  Bacteriologically  the  presence  of 
extra -cellular  meningococci  marks  the  grave  but  not  necessarily  fatal 
character  of  the  case.  The  older  physicians  laid  considerable  stress  on 
the  presence  of  herpes  and  of  a  macular  rash,  appearing  late,  as  signs 
of  favourable  prognostic  import.  The  pith  of  this  observation  probably 
lies  in  the  fact  that  both  these  symptoms  are  late  in  appearance,  from 
the  third  to  the  sixth  day,  a  period  at  which  the  immediate  issue  of  the 
case  is  already  largely  decided.  In  our  experience  the  presence  of 
herpes  is  a  fallacious  guide,  some  of  our  most  fatal  cases  presented 
a  marked  herpetic  eruption.  With  regard  to  a  macular  rash,  in  our 
experience  no  case  which  presented  this  rash  was  immediately  fatal, 
although  some  died  subsequently  of  hydrocephalus. 

The  date  at  which  treatment  is  begun  is  a  factor  of  great  importance 
in  prognosis.  When  drainage  can  be  established  on  the  first  or  second 
day,  in  other  than  fulminating  cases  the  prognosis  is  good.  On  the 
other  hand  should  treatment  not  be  undertaken  until  the  fourth  or 
fifth  day  or  later,  there  is  always  the  possibihty  that  the  power  of 
reaction  of  the  patient  may  have  become  exhausted,  or  that  an  exudation 
has  already  formed  which  may  lead  to  hydrocephalus. 

The  age  of  the  patient  forms  some  basis  for  a  forecast,  in  that  the 
mortaUty  rate  of  an  epidemic  follows  a  more  or  less  defined  curve  in 
relation  to  the  age  at  which  the  cases  are  attacked.  The  greatest 
mortaUty  occurs  in  infants  imder  two  years  of  age ;  after  two  years  of 
age,  it  begins  to  dechne  imtil  about  the  fifteenth  year.  Netter  regards 
the  death  rate  as  lowest  from  the  seventh  to  the  fifteenth  year.  After 
the  fifteenth  year  the  rate  increases  somewhat,  to  fall  sUghtly  in  the 
decade  from  twenty  to  thirty.  After  thirty  it  rises  abruptly  and  con- 
tinues to  rise  with  each  decade  of  fife.  Our  own  experience,  which 
included  all  the  cases  drawn  from  troops  quartered  in  the  counties  of 
Cambridge  and  the  Isle  of  Ely,  Huntingdon,  Bedford,  Northampton, 
Hertford  and  part  of  Buckingham,  yields  the  following  results.  Cases 
occurring  in  men  between  17  and  22  were  23  in  number,  of  whom 
9  died,  a  mortahty  rate  of  40  per  cent.  Between  the  ages  of  22  and  30, 
there  were  13  cases,  of  whom  2  died,  a  mortahty  rate  of  15  per  cent. 
Four  cases  occurred  in  men  between  34  and  45,  of  whom  3  died,  a 
mortahty  rate  of  75  per  cent.  From  these  figures  it  woidd  appear  that 
the  chances  of  recovery  materially  increase  when  full  maturity  is  reached. 
After  the  age  of  thirty,  the  chances  of  recovery  markedly  diminish. 


vi]  Course  and  Prognosis  69 

The  prognostic  value  to  be  attached  to  the  age  of  the  patient  is  of 
subsidiary  importance,  but  may  serve  to  introduce  an  element  of  caution 
in  giving  a  favourable  or  unfavourable  opinion. 

The  stage  of  the  epidemic,  at  which  the  patient  is  attacked,  may  be 
taken  into  account  in  forming  a  forecast  of  the  probable  course  of  the 
disease.  It  is  stated  by  Netter  and  others  that  there  are  more  fulmin- 
ating and  severe  cases  at  the  beginning  of  an  epidemic,  and  that  the 
later  cases  assume  a  mild  or  abortive  type.  That  the  final  stage  of 
an  epidemic  is  marked  by  a  mild  type  of  the  disease  is  incontestable. 
The  period  of  maximum  intensity  as  regards  virulence  of  type  is, 
however,  not  so  definitely  estabhshed.  Our  own  experience  does  not 
bear  out  the  view  that  the  earlier  cases  present  the  most  dangerous 
type.  All  the  cases,  forty-eight  in  number,  occurring  during  the  first 
six  months  of  the  year  1915  amongst  troops  quartered  in  the  five  and 
a  half  counties  already  mentioned,  have  been  collected.  This  includes 
eight  cases  which  were  not  treated  by  us.  These  cases  with  their 
relative  mortality  have  been  tabulated  by  months.  The  accompanying 
table  shews  the  relative  virulence  of  the  epidemic  in  each  month,  as 
evidenced  by  percentage  mortaUty. 


Deaths  taking 

place  before 

Percentage 

Month 

Cases 

Deaths 

the  fifth 

day 

mortality 

January 

4 

0 

0 

0 

February 

12 

5 

4 

41 

March 

15 

7 

4 

47 

April 

9 

7 

5 

77 

May 

4 

1 

1 

25 

June 

4 

1 

0 

25 

From  this  table  it  wiU.  be  seen  that  the  onset  of  the  epidemic  was 
marked  by  a  series  of  mild  cases.  The  virulence  then  steadily  increased 
until  April.  The  subsequent  two  months  shew  an  abrupt  dechne  in 
the  percentage  of  fatal  cases.  A  further  study  of  our  records  accentuates 
the  culminating  period  of  virulence  and  its  abrupt  dechne.  The  first 
14  days  of  April  yielded  8  cases  with  7  deaths,  a  mortahty  percentage 
of  87.  In  5  cases  death  took  place  in  imder  5  days.  In  the 
following  6  weeks  there  were  9  cases  with  2  deaths,  a  mortahty  per- 
centage of  22.  One  case  died  in  under  5  days.  These  figures  demon- 
strate the  fact  that  the  virulence  of  the  epidemic  steadily  increased, 
until  the  acme  was  reached  in  April.  From  that  time  a  very  abrupt 
decline  in  mortahty  took  place.  As  further  evidence  of  the  mild 
character  of  the  later  cases  in  the  epidemic,  it  may  be  noted  that,  in 
the  four  months  subsequent  to  the  1st  of  July,  three  cases  have  been 


70  Course  and  Prognosis  [oh. 

admitted  with  hydrocephalus,  from  which  they  died.  In  these  cases 
the  primary  stage  of  the  disease  had  been  so  Uttle  defined  as  to  give 
rise  to  error  in  diagnosis.  In  so  far  as  any  aid  to  prognosis  can  be 
obtained  from  these  figures,  the  conclusion  would  be  that,  until  a  marked 
dechne  in  virulence  had  been  established,  the  later  in  the  epidemic  the 
individual  was  attacked,  the  greater  the  probable  severity  of  the  disease. 
As  has  frequently  been  insisted  upon,  the  remote  prognosis  of 
cerebro-spinal  fever  is  usually  good.  Allusion  has  already  been  made 
to  the  possibihty  of  imbecility  following  posterior  basic  meningitis  in 
infants.  In  the  adult  it  might  be  conjectured  that  a  disease,  the  essential 
features  of  which  are  dependent  on  prolonged  cerebral  compression, 
could  not  fail  to  leave  behind  some  impress  on  the  mental  condition 
of  the  patient.  The  further  the  subject  is  pursued,  the  more  evident 
does  the  extreme  rarity  of  mental  enfeeblement  as  a  sequela  become. 
Netter,  in  a  chapter  of  great  hterary  charm,  entitled  "L'Avenir  du 
Meningitique "  affirms  his  conviction  that  no  such  enfeeblement  occurs. 
Our  own  experience  entirely  confirms  this  view,  in  none  of  our  cases 
was  there  any  enfeeblement  of  the  mental  powers  when  complete  re- 
covery had  taken  place.  Not  only  were  the  mental  powers  unaffected, 
but  no  change  in  the  moral  balance  of  the  patients,  as  evidenced  by 
waywardness  or  moroseness,  was  observed.  In  the  Hitchin  Home  for 
soldiers  convalescent  from  cerebro-spinal  fever,  out  of  thirty-two  inmates 
drawn  from  all  over  the  country,  only  one  case  shewed  any  signs  of 
mental  change.  In  this  case  there  was  complete  loss  of  memory,  but, 
as  concomitant  palsy  of  the  right  arm  was  present,  the  defect  would 
appear  to  owe  its  origin  to  a  locahzed  cortical  lesion,  rather  than  to 
psychical  degeneration.  At  a  subsequent  visit  six  months  later  his 
memory  was  almost  completely  restored,  though  some  feebleness  of 
the  arm  still  remained. 

Headache  may  continue  for  some  time  when  convalescence  is  well 
established  and  Kernig's  sign  is  absent.  In  common  with  the  majority  of 
post-febrile  nervous  affections,  this  symptom  entirely  disappears  within  a 
few  months.  Deafness  may  disappear  at  the  end  of  two  or  three  months, 
but  in  a  certain  number  of  cases  the  patient  remains  totally  and  incurably 
deaf.  In  the  extremely  rare  cases  in  which  blindness  results  in  adults, 
it  is  due  to  optic  atrophy  and  is  permanent  and  incurable.  A  locahzed 
palsy  either  of  one  of  the  cranial  nerves  or  of  a  hmb  may  persist  for 
some  months  after  convalescence  is  estabhshed.  If  the  case  be  followed 
up,  the  palsy  will  almost  invariably  be  found  to  have  disappeared. 
Restoration  of  function  may  not,  however,  be  complete  for  many  months. 


vi]  Course  and  Prognosis  71 

Other  symptoms  which  persist  for  a  long  time  are  pains  in  the  back  and 
legs ;  the  pain  and  stiiiness  of  the  back  with  its  accompanying  awkward 
gait  may  persist  for  many  months.  Some  of  our  patients,  who  were 
far  too  good  soldiers  to  be  suspected  of  mahngering,  were  totally  unable 
to  march  with  a  pack  for  three  or  four  months  after  rejoining  their 
regiments.     In  all  cases  this  disabihty  eventually  disappears. 

Sequelae  other  than  those  pertaining  to  the  nervous  system  are 
practically  unknown.  In  contrast  to  other  fevers,  the  heart  muscle 
is  entirely  unaffected.  Endocarditis  has  been  described  as  a  sequela, 
but  its  occurrence  is  infinitely  rare.  The  kidneys  are  entirely  unafEected, 
the  transient  febrile  albuminuria  completely  disappearing.  It  must  be 
remembered  that  the  differentiation  of  the  gonococcus  and  meningo- 
coccus is  extremely  difficult,  therefore  accounts  of  metastatic  foci  due 
to  meningococcal  infection  must  be  received  with  caution. 

The  comparative  rarity  of  sequelae  in  the  recent  epidemics  affords 
a  curious  contrast  to  their  apparent  frequency  in  those  of  the  past. 
Through  all  the  writings  of  the  older  physicians  there  runs  the  same 
note  of  warning,  that  many  of  the  survivors  would  suffer  some  permanent 
infirmity.  This  conclusion  was  reached  after  experience  of  epidemics  in 
which  aduJts  and  children  were  alike  stricken,  and  cannot  have  been 
prompted  by  observing  cases  of  posterior  basic  meningitis  alone.  The 
explanation  of  this  change  of  view  would  appear  to  be  a  twofold  one. 
In  the  first  place  cases  of  the  cerebral  form  of  acute  anterior  poho- 
myehtis  were  probably  not  differentiated:  in  consequence  subsequent 
palsies  due  to  this  disease  were  attributed  to  cerebro-spinal  fever. 
In  the  second  place  the  tension  of  the  cerebro-spinal  fluid  was  entirely 
unreheved  by  the  older  methods  of  treatment.  Whatever  method  of 
treatment  has  been  adopted  in  later  years,  the  theca  has  usually  been 
punctured.  Consequently,  in  cases  occurring  in  the  latter  epidemics, 
the  nervous  elements  have  not  been  exposed  to  the  same  prolonged 
pressure  as  was  the  case  in  earher  outbreaks. 

The  absence  of  chronic  nervous  sequelae  in  the  latter  epidemics, 
compared  to  their  relative  prevalence  in  past  times,  goes  far  to  strengthen 
the  view  that  their  essential  cause  was  prolonged  pressure.  Netter, 
Flexner  and  Sophian  attribute  apparent  diminution  in  the  frequency 
of  sequelae  and  their  lessened  gravity  to  the  employment  of  serum. 
That  serum  alone  is  the  determining  factor  may  be  questioned,  since 
our  own  cases  also  shewed  a  singular  absence  of  sequelae.  In  the 
majority  of  these  adequate  drainage  by  lumbar  puncture  methodically 
repeated  was  the  only  method  of  treatment. 


CHAPTER  VII 

TREATMENT 

Fatal  nature  of  the  disease.  Early  methods  of  treatment,  their 
failure.  Introduction  of  serum  treatment,  researches  of  Flexner 
and  Jochmann,  diminished  mortality.  Serum  treatment  in  the 
epidemic  of  1915,  statistics  of  First  Eastern  General  Hospital. 
Treatment  by  lumbar  puncture  alone.  The  dangers  of  serum  treatment, 
the  procedure  to  be  adopted,  dosage  to  be  employed,  indications  for 
suspension  of  treatment.  Method  of  simple  lumbar  puncture,  its 
comparative  safety,  indications  for  the  continuance  of  treatment, 
possible  sequelae.  Treatment  by  other  methods,  vaccines,  soamin, 
hexamine.  General  treatment,  nursing,  food,  drugs,  operative  treat- 
ment. 

The  statistics  of  the  earlier  epidemics  manifest  the  extremely  fatal 
nature  of  cerebro-spinal  fever.  This  mortality  varied  sensibly  according 
to  the  nature  of  the  epidemic,  but  even  outbursts  of  a  mild  type  stamp 
cerebro-spinal  fever  as  one  of  the  most  fatal  of  all  diseases.  Methods 
of  treatment  innumerable  succeeded  one  another,  their  adoption  being 
largely  influenced  by  the  pathological  views  current  at  the  time.  The 
antiphlogistic  method  of  treatment,  in  vogue  at  the  date  of  the  first 
recognition  of  the  disease,  remained  in  fashion  to  some  extent  till  recent 
times.  In  a  disease  so  obviously  desperate,  and  in  which  the  hope  of 
arrest  by  natural  means  was  so  slight,  it  was  held  that  none  but  active 
measures  were  likely  to  be  of  any  avail.  Consequently  venesection 
from  the  arm  or  the  jugular  vein  was  practised  in  all  cases.  In  addition 
leeches  to  the  head,  blisters  to  the  scalp  and  neck,  dry  and  wet  cupping 
to  the  spine,  were  all  used  as  auxiliary  methods  of  treatment.  iWercury 
was  pushed  to  salivation  either  by  the  mouth  or  inunction.  The 
administration  of  emetics  completed  the  tale  of  active  measures.  In 
spite  of  these  heroic  methods  the  death  rate  of  the  disease  remained  as 
high  as  ever.  As  conceptions  of  treatment  changed,  the  administration 
of  drugs  and  soothing  remedies  succeeded  the  more  violent  procedures 
of  a  former  generation.     The  apphcation  of  ice  to  the  head,  or  Leiter's 


CH.  vn]  Treatment  73 

cap,  to  allay  cerebral  inflammation,  tlie  administration  of  iodide  of 
potassium  to  promote  absorption,  and  the  use  of  opium  to  relieve 
pain  were  extensively  employed.  The  immersion  of  the  patient  two 
or  three  times  a  day  in  a  warm  bath  undoubtedly  conferred  great  relief 
to  symptoms.  With  these  milder  methods  of  treatment,  the  patient's 
sufferings  were  doubtless  lessened  and  his  strength  husbanded,  but  no 
appreciable  effect  was  produced,  upon  the  death  rate. 

As  an  index  of  the  apparent  failure  of  treatment,  the  statistics  of 
the  epidemic  of  1904-5  may  serve  as  an  illustration.  It  must  be 
borne  in  mind  that  these  statistics  refer  to  a  time  when  the  causative 
organism  of  the  disease  had  been  isolated  and  great  strides  had  been 
made  in  pathological  knowledge.  The  figures  for  New  York  City, 
according  to  Heiman  and  Feldstein,  were  4000  cases  with  3429  deaths : 
a  mortality  of  86  per  cent.  The  records  of  the  children's  hospital 
in  Boston,  where  every  case  was  bacteriologically  confirmed,  show, 
according  to  Dunn,  a  mortality  varying  from  70  per  cent,  in  1902, 
to  90  per  cent,  in  1907.  In  the  Belfast  epidemic  during  the  eighteen 
months  ending  January  1908  there  were  725  cases  with  548  deaths: 
a  death  rate  of  76  per  cent.  Ker,  during  the  same  epidemic  in 
Edinburgh,  had  108  cases  with  87  deaths:  a  mortality  percentage  of 
80.  These  statistics  shew  that,  up  to  this  point,  scientific  research  had 
failed  to  secure  any  therapeutic  method  which  was  practically  more 
successful  than  the  antiphlogistic  measures  of  our  grandfathers.  But 
the  labour  spent  in  years  of  pathological  research  was  soon  to  bear 
fruit.  In  1905  Flexner  in  America  and  Jochmann  in  Germany  began 
a  series  of  researches  on  the  possibihty  of  producing  a  serum  which 
would  be  bactericidal  to  the  meningococcus.  Experiments  were  first 
made  on  small  animals  in  the  laboratory.  As  a  result  of  his  investiga- 
tions Flexner  produced  a  serum  which  rendered  small  animals  immune 
to  lethal  doses  of  culture  of  the  meningococcus.  He  next  produced 
a  serum  from  goats  which,  when  injected  intrathecally  into  monkeys, 
was  protective  to  injections  of  live  cultures  of  the  meningococcus. 
A  control  animal  which  received  no  serum  died.  Jochmann  also 
produced  a  serum  which  experimentally  was  demonstrated  to  possess 
bactericidal  properties.  Flexner,  continuing  his  researches  by  means  of 
injecting  horses  with  both  dead  and  live  cultures,  finally  produced  an 
anti-serum  of  demonstrable  value.  To  Flexner  must  be  assigned  the 
credit  of  selecting  the  intrathecal  method  of  adrm'nistering  the  serum 
in  preference  to  its  subcutaneous  or  intravenous  injection.  He  con- 
cluded that  by  this  means  the  direct  action  of  the  concentrated  serum  on 


LIBRARY  CP  THE 

COLUMBIA  UNiyEi<srry 
NEW  YORK 


74  Treatment  [CH. 

the  organisms  in  situ  would  be  more  eSective  than  the  weak  action  of 
the  dilute  concentration,  which  the  blood  stream  conveys.  The  results 
achieved  by  the  chnical  use  of  Flexner's  serum  stamped  it  as  one  of  the 
most  remarkable  achievements  of  experimental  medicine.  With  the 
exception  of  the  introduction  of  diphtheria  anti-toxin,  no  discovery  in 
the  domain  of  pure  Physic  has  yielded  such  striking  and  beneficent 
results.  Flexner's  serum  was  first  used  at  Akron  in  the  State  of  Ohio 
in  May  1907.  In  this  epidemic,  of  9  cases  not  treated  with  serum, 
8  or  89  per  cent.  died.  Conversely,  of  11  cases  treated  with  serum, 
3  only,  or  27  per  cent.  died.  Further  experience  of  the  use  of 
Flexner's  serum  served  only  to  confirm  and  amplify  this  astonishing 
success.  In  1913  Flexner  published  an  analysis  of  1294  cases.  Of 
these  cases,  400  died,  giving  a  mortahty  rate  of  30  per  cent.  In  the 
United  Kingdom,  Gardner  Robb  at  Belfast  found  that,  after  the  use  of 
Flexner's  serum,  the  mortality  percentage  fell  from  85  to  26. 

Up  to  the  year  1915  epidemics  of  cerebro-spinal  fever,  with  a  few 
trifling  exceptions,  had  been  confined  to  three  or  four  large  cities  in 
Scotland  and  Ireland.  In  the  beginning  of  1915  an  epidemic  spread 
over  the  greater  part  of  England,  notably  amongst  the  large  bodies  of 
troops  then  undergoing  training.  '  Great  hopes  were  entertained  that 
the  employment  of  Flexner's  serum  would  shew  still  further  success. 
The  results  attained  were,  however,  in  a  large  measure  disappointing. 
Of  purely  military  cases,  the  outbreak  in  the  Canadian  contingent 
on  Salisbury  plain,  the  first  in  point  of  time,  may  be  considered. 
Osier  states  that  there  were  40  cases  with  26  deaths,  a  mortality 
percentage  of  65.  The  statistics  for  the  Royal  Navy,  as  given  by 
Surgeon  General  RoUeston,  furnish  the  following  data.  The  total 
number  of  cases  was  170,  of  which  the  notes  of  163  had  been  abstracted. 
The  death  rate  of  the  whole  series  was  53  per  cent.  Cases  treated  by 
serum  were  105  in  number,  of  whom  64  died,  a  mortahty  percentage 
of  60.  In  civilian  practice,  Gardner  Robb  at  Belfast  had  100  cases, 
all  treated  by  serum,  with  36  deaths,  or  a  mortality  percentage  of  36. 
Robb  further  remarks  that  he  beheves  no  case  in  the  North  of  Ireland, 
which  was  not  treated  by  serum,  recovered.  Our  own  experience  was 
confined  to  soldiers  treated  in  the  First  Eastern  General  Hospital. 
The  first  case  which  came  under  our  care  was  that  of  a  soldier  found 
unconscious  in  bed,  .profoundly  comatose,  with  general  twitchings.  As 
no  serum  was  available,  lumbar  puncture  was  performed,  and  repeated 
on  the  two  following  days.  After  the  third  puncture  the  patient 
regained  consciousness  and  made  a  rapid  and  uninterrupted  recovery. 


vn]  Treatment  75 

Two  other  cases,  admitted  a  day  or  two  later,  both  recovered  after 
treatment  by  lumbar  puncture  alone.  Treatment  by  serum  was  then 
begun,  with  the  following  results.  Seven  consecutive  cases  were  treated 
with  serum  in  the  hospital,  and  two  had  received  injections  elsewhere 
before  admission.  Of  these  nine  cases  five  died,  a  mortahty  per- 
centage of  55.  Considering  the  unfavourable  results  obtained  with 
serum  treatment,  and  the  success  which  had  attended  simple  lumbar 
puncture  in  the  earher  cases,  it  was  determined  to  give  the  latter  method 
a  further  trial.  Our  final  results  from  January  20th  to  June  15th, 
during  which  time  we  had  joint  charge  of  the  ward  set  apart  for  these 
cases,  are  shewn  in  the  following  table. 


Cases 

Recovered 

Died 

Percentage 
mortality 

Total  number     

39 

25 

14 

36-0 

Treated  with  serum  . . . 

9 

4 

5 

550 

Treated  without  serum 

30 

21 

9 

30-0 

These  cases  were  drawn  from  the  district  in  which  we  were  responsible 
for  diagnosis  and  treatment,  which  comprised  the  counties  of  Cambridge 
and  the  Isle  of  Ely,  Huntingdon,  Bedford,  Northampton,  Hertford  and 
part  of  Buckingham.  In  this  district  seven  other  cases  occurred  which 
were  not  admitted  into  the  hospital.  Of  these  six  died  and  one 
recovered.  This  gives  a  total  for  the  troops  in  the  district  of  46  cases 
with  20  deaths,  a  percentage  of  43.  Four  of  these  cases  were  treated 
outside,  of  which  three  were  fatal,  being  attacked  before  accommo- 
dation had  been  systematically  provided  at  the  First  Eastern  General 
Hospital.  Of  the  remaining  three  cases,  one  was  found  dead,  the  other 
two  were  not  recognized  until  a  few  hours  before  death.  These  cases 
may  be  regarded  as  virtually  untreated.  As  we  were  denied  the 
opportunity  of  deahng  with  these  cases,  we  have  excluded  them  from 
our  discussion  on  treatment.  A  study  of  the  above  table  demonstrates 
the  want  of  success  attending  treatment  with  serum,  as  contrasted 
with  the  comparative  success  attending  simple  lumbar  puncture.  The 
number  of  cases  is  small  for  purposes  of  comparison  with  the  results  of 
other  observers;  but  within  this  limitation  the  following  comparison 
can  be  made.  Flexner  in  his  report  on  serum  treatment,  pubhshed  in 
1913,  states  that  288  patients  over  20  years  of  age  had  been  treated 
with  108  deaths,  a  mortahty  of  37  per  cent.  Of  our  own  cases,  24  were 
over  20  years  of  age;  of  these  8  died,  giving  a  mortahty  percentage 
of  33.  Twenty  of  these  cases,  however,  were  treated  by  lumbar 
puncture  alone,  with  4  deaths,  a  mortahty  percentage  of  20.     In  as 


76  Treatment  [ch. 

far  as  small  numbers  can  afford  ground  for  judgment,  the  results  of 
simple  lumbar  puncture  will  bear  comparison  with  the  results  obtained 
by  serum  treatment  in  former  epidemics. 

The  comparative  failure  of  serum  treatment  in  this  epidemic  is 
obvious  from  a  study  of  the  results  obtained  in  widely  separated 
locahties.  The  mortality  percentage  of  serum-treated  cases  in  the 
Eoyal  Navy  was  60,  while  in  ours  it  was  55.  This  disposes  of  the 
argument  that  the  comparative  virulence  of  the  epidemic  might  have 
marked  local  variations.  It  has  been  suggested  by  Osier  and  Robb 
that  the  sera  available  were  feeble  in  their  action  owing  to  the  sudden 
call  made  on  their  production.  It  has  further  been  surmised  that 
strains  of  organisms  may  have  been  involved  in  this  epidemic  markedly 
different  from  those  of  the  earher  ones.  Thus  the  polyvalent  sera  used 
for  treatment  did  not  correspond  with  the  infective  organism.  The 
want  of  general  success  attending  the  subcutaneous  use  of  the  serum 
of  Jochmann,  as  contrasted  with  the  intrathecal  method  advocated 
by  Flexner,  has,  in  the  opinion  of  some  authors,  been  due  to  their 
method  of  administration.  Flexner  from  the  first  claimed  that  the 
concentration  of  the  bactericidal  effect  of  serum  administered  intra- 
thecally  ensured  more  efficient  action,  when  it  reached  the  meninges, 
than  in  the  more  dilute  form  conveyed  by  the  blood  stream.  The 
intrathecal  injection  of  serum,  however,  involves  two  separate  pro- 
cedures, firstly,  the  free  evacuation  of  the  cerebro-spinal  fluid,  and 
secondly,  the  injection  of  serum.  It  may  be  conjectured  that  the  free 
drainage,  which  thus  forms  such  an  integral  part  of  serum  treatment, 
may  be  in  some  measure  responsible  for  the  marked  success  of  this 
method  over  all  previous  ones.  Dr  David  Morgan  of  Swansea  pub- 
hshed  in  1909  his  experience  of  the  epidemic  occurring  in  that  place 
during  1908.  During  the  whole  outbreak  63  cases  occurred,  out  of 
which  number  50  died,  a  mortality  percentage  of  79.  Of  this  number, 
45  cases  were  treated  in  their  own  homes,  of  whom  42  died,  a  mortality 
percentage  of  93.  A  striking  contrast  to  these  figures  was  afforded 
by  the  result  obtained  at  the  Borough  Fever  Hospital,  where  18  cases 
were  treated  with  only  8  deaths,  a  mortality  percentage  of  44.  The 
method  of  treatment  employed  in  the  hospital  cases  was  repeated 
lumbar  puncture,  perforn;ed  daily  if  necessary.  In  cases  treated  in 
their  own  homes,  considerable  difficulty  was  experienced  in  obtaining 
the  consent  of  parents  or  friends  to  the  performance  of  lumbar 
puncture,  which  was  therefore  only  performed  for  diagnostic  purposes. 
The  two  categories  of  cases  represent  fairly  accurately  the  difference 


vii]  Treatment  77 

between  treatment  by  lumbar  puncture  and  the  results  of  non- 
interference. This  contrast  is  sufficiently  striking,  the  effects  of 
treatment  shewing  a  reduction  of  the  death-rate  by  nearly  50  per 
cent.  It  must  be  borne  in  mind  that  these  results  were  pubhshed  at 
the  time  when  serum  treatment  was  first  introduced.  In  commenting 
on  his  results,  Morgan  remarks  that,  had  serum  been  used,  the  notable 
reduction  in  the  death  rate  would  have  been  attributed  to  its  effects. 
Further,  he  calls  attention  to  the  fact  that  lumbar  puncture,  with  the 
evacuation  of  a  considerable  quantity  of  fluid,  is  an  essential  preliminary 
to  the  injection  of  serum.  This,  in  his  opinion,  raises  the  question  as 
to  how  far  the  beneficial  effects  of  serum  treatment  may  not  be  due 
to  the  preliminary  lumbar  puncture.  We  would  submit  that  the  results 
which  we  have  obtained  materially  strengthen  the  pertinence  of  this 
query. 

The  injection  of  serum  involves  on  the  one  hand  the  introduction 
of  a  foreign  proteid,on  the  other  the  replacement  of  fluid,  with  consequent 
return  of  the  pressure  which  has  just  been  reheved.  The  conjecture, 
that  the  presence  of  a  foreign  proteid  may  exercise  toxic  effects  on  the 
brain,  is  borne  out  by  the  not  infrequent  subsequent  increase  of  headache 
and  rise  of  temperature,  the  latter  symptom  being  in  marked  contrast 
to  the  decided  fall  of  temperature  which  follows  lumbar  puncture. 
Experience  has  proved  that  the  replacement  of  fluid,  if  carried  to  an 
extreme,  may  have  the  most  alarming  consequences.  Sophian's  studies 
on  blood  pressure  shew  that  the  introduction  of  serum  above  an  amount, 
which  varies  in  each  individual  case,  may  cause  a  sudden  fall  in 
blood  pressure  with  signs  of  extreme  collapse.  He  also  finds  that  the 
injection  of  even  small  quantities  of  serum  causes  an  appreciable  fall 
in  blood  pressure.  He  further  states  that  alarming  hydrocephalic 
symptoms  may  arise  at  an  interval  of  some  hours  after  the  injection 
of  serum.  In  our  somewhat  limited  experience,  the  introduction  of 
serum  caused  for  the  most  part  a  decided  aggravation  of  cerebral 
symptoms.  From  these  data  it  is  obvious  that  both  immediate  and 
comparatively  remote  effects  may  follow  the  injection  of  serum.  The 
fall  of  temperature  and  relief  of  cerebral  symptoms,  which  follow  simple 
lumbar  puncture,  afford  a  striking  contrast.  Whether  this  difference 
depends  on  purely  mechanical  causes,  or  on  conditions  of  fluid  inter- 
change, or  again  on  a  direct  toxic  effect  arising  from  the  serum,  is  a 
matter  for  further  enquiry.  The  essential  point  remains  that,  whatever 
the  bactericidal  action  of  serum  may  be,  its  use  is  attended  by  certain 
immediate  disadvantages.     As  is  described  elsewhere,  the  agglutinative 


78  Treatment  [CH. 

power  of  the  patient's  own  serum  is  in  many  cases  far  greater  than 
that  of  artificially  prepared  anti-meningococcal  serum.  This  fact  was 
put  to  practical  use  in  one  of  our  cases.  A  man,  who  had  recovered 
from  all  acute  symptoms,  suffered  from  irregular  attacks  of  fever 
accompanied  by  headache.  Five  c.c.  of  his  own  serum  was  injected 
intrathecally,  and  complete  relief  of  all  his  symptoms  ensued.  It  is 
possible  that  further  observations  in  this  direction  may  lead  to  fresh 
methods  of  serum  treatment.  At  present,  the  whole  question  is  a  matter 
for  further  investigation  and  discussion,  before  any  dogmatic  statement 
can  be  made  as  to  the  value  of  serum  in  assisting  lumbar  pvmcture. 

With  regard  to  treatment  by  lumbar  puncture,  it  has  the  great 
merit  that  it  can  be  used  at  once,  and  under  any  circumstances.  The 
experience  of  the  use  of  simple  lumbar  puncture  by  Morgan  and  our- 
selves justifies  the  statement  that  lumbar  puncture  should  never  be 
delayed  because  no  serum  is  available.  The  statement,  made  by 
Flexner  and  others  that  the  prognosis  depends  very  largely  on  the 
injection  of  serum  at  the  earhest  possible  date,  apphes  with  even 
greater  force  to  the  imperative  necessity  of  lumbar  pimcture  at  the 
earhest  possible  moment.  It  must  be  clearly  understood  that  the 
operation  of  lumbar  pimcture  does  not  merely  imply  the  removal  of 
a  small  quantity  of  fluid,  but  a  thorough  evacuation  of  all  excess  of 
fluid  in  the  sub-arachnoid  space. 

When  it  has  been  decided  to  inject  serum  the  earUer  procedure  is 
identical  mth  the  operation  of  lumbar  puncture,  which  has  already 
been  described  in  deaUng  with  diagnosis.  When  as  much  fluid  as 
possible  has  been  run  off,  the  lumbar  puncture  needle  is  left  in  situ 
for  the  subsequent  insertion  of  serum.  The  introduction  of  the  serum 
can  be  accompUshed  in  two  ways;  either  by  the  force  of  gravity,  or 
by  means  of  a  syringe.  The  essential  point  to  be  borne  in  mind  is 
that  the  introduction  of  serum  is  an  operation  by  no  means  devoid  of 
danger.  Whichever  method  is  adopted,  the  injection  must  be  made 
extremely  slowly,  at  least  ten  minutes  should  be  taken  in  injecting 
15  c.c.  The  apparatus  required  for  the  gravity  method  is  a  funnel  with 
about  two  feet  of  india-rubber  tubing  provided  with  a  chp.  The 
tubing  should  be  in  two  pieces,  connected  by  a  piece  of  glass  tubing 
whereby  the  flow  of  the  serum  can  be  observed.  The  distal  end  of  the 
tubing  fits  on  to  the  lumbar  puncture  needle.  Some  of  the  American 
sera  are  sent  out  in  phials,  each  pro\aded  with  a  suitable  length  of 
tubing  which  fits  into  the  lumbar  pimcture  needle,  the  phial  itself  can 
then  be  utihzed  as  a  funnel.     The  chp  should  be  used  to  secure  the  distal 


vn]  Treatment  79 

end  of  the  tube  before  connecting  with  the  puncture  needle.  The 
tubing  and  funnel  should  be  boiled.  As  has  been  before  stated,  a 
general  anaesthetic  is  advisable  and  free  from  any  special  danger. 
When  as  much  fluid  as  will  readily  flow  has  been  removed,  the  tubing 
is  connected  with  the  needle  and  the  cUp  removed.  The  serum 
should  previously  have  been  brought  to  body  heat  by  immersion  in 
warm  water.  The  funnel  is  then  raised,  and  the  fluid  allowed  to  flow. 
The  funnel  should  be  kept  at  a  height  of  eighteen  inches,  which  will 
ensure  that  the  flow  is  sufficiently  slow.  When  the  syringe  is  used, 
it  should  not  be  connected  directly  with  the  puncture  needle  but 
joined  by  a  piece  of  tubing,  provided  with  a  glass  inset.  The  in- 
jection should  be  made  extremely  slowly.  As  a  rough  rule,  counting 
twenty  between  the  slow  injection  of  each  half  c.c.  will  ensure 
sufficient  gentleness  in  the  injection.  When  the  injection  is  finished, 
the  pimcture  should  be  covered  by  gauze  and  collodion.  The  foot 
of  the  bed  should  then  be  raised  on  blocks  to  a  height  of  a  foot, 
in  order  to  help  the  diffusion  of  the  serum  by  means  of  gravity. 
During  the  administration  the  condition  of  the  pulse  and  respiration 
must  be  carefully  watched.  If  the  pulse  becomes  intermittent  or 
thready,  or  the  respirations  shallow  or  irregular,  the  injection  miist  be 
stopped  at  once.  It  must  be  borne  in  mind  that  it  is  an  absolute  rule 
that  more  fluid  should  previously  be  removed  than  the  quantity  of 
serum  injected.  If  the  cerebro-spinal  fluid  is  allowed  to  flow  freely, 
the  amount  removed"  will  be  far  in  excess  of  the  quantity  of  serum 
likely  to  be  injected.  Too  much  insistence  cannot  be  laid  on  the 
danger  attending  the  injection  of  an  amount  of  serum  equal  to  the 
quantity  of  cerebro-spinal  fluid  removed.  If  due  care  be  not  exercised 
in  this  regard,  a  rise  of  cerebro-spinal  pressure  may  be  induced  which 
may  act  directly  on  the  medulla.  Any  symptom  of  vagus  inhibition, 
or  the  occurrence  of  Cheyne-Stokes  breathing,  or  changes  in  the  pupils, 
should  be  a  signal  for  immediately  stopping  the  injection.  Sophian 
has  made  a  series  of  observations  on  the  effect  of  the  injection  of  serum 
on  blood  pressure.  From  the  cHnical  data  thus  obtained,  he  concludes 
that  the  variations  in  blood  pressure  can  afford  guidance  during  the 
operation  of  injection.  During  the  removal  of  fluid,  the  effect  on  the 
blood  pressure  is  by  no  means  constant,  a  sKght  drop  of  3-10  milh- 
metres  being  the  more  common  result.  With  the  injection  of  serum, 
however,  there  is  an  initial  fall  in  blood  pressure  which  is  steadily 
maintained  while  the  injection  continues.  After  the  blood  pressure  has 
fallen  20-30  mm.  any  further  injection  of  serum  usually  gives  rise  to 


80  Treatment  [ch. 

a  larger  and  more  rapid  drop,  even  the  addition  of  2  or  3  c.c.  may 
cause  a  sudden  fall  of  40  mm.  Such  a  sudden  fall  may  be  followed 
either  immediately  or  in  a  few  minutes  by  the  supervention  of  alarming 
indications  of  collapse.  In  some  of  Sophian's  cases,  in  which  injection 
has  been  persevered  with  after  the  initial  fall  in  blood  pressure, 
the  breathing  became  shallow,  the  pulse  became  impalpable,  and 
all  the  signs  of  impending  death  by  shock  developed.  Under  these 
circumstances,  in  addition  to  stimulating  measures,  as  much  fluid  as 
possible  should  be  allowed  to  run  out  from  the  theca.  As  a  further 
result  of  this  most  careful  investigation,  Sophian  has  been  led  to 
reduce  materially  the  amount  of  serum  injected.  The  main  danger  to 
be  guarded  against  is  death  from  shock  during  the  injection  of  the 
serum;  more  remote  dangers  are  of  a  minor  character.  Surgeon 
General  Rolleston  states  that  anaphylactic  symptoms  were  never  of 
a  serious  character.  A  serum  rash  may  appear  about  the  ninth  or 
tenth  day;  this  is  frequently  urticarial,  but  sometimes  papular.  The 
rash  may  be  accompanied  by  pains  in  the  joints,  which  are  the  usual 
signs  of  the  so-called  serum  disease. 

Opinion  differs  materially  as  to  the  dosage  of  serum  to  be  employed. 
Netter  insists  upon  the  necessity  of  an  initial  large  dose,  40  c.c.  for  an 
adult,  followed  by  a  smaller  dose  of  20-30  c.c.  on  the  next  two  or  three 
days.  He  further  insists  on  the  routine  practice  of  injection  for  the  first 
three  or  four  days,  no  matter  how  great  the  signs  of  improvement  have 
been.  The  sum  total  of  doses  given  to  an  individual  patient  may 
amount  to  700-800  c.c.  Sophian  as  the  result  of  his  observations  on 
blood  pressure  was  led  to  the  conclusion  that  smaller  doses  than  he 
had  hitherto  employed  were  advisable.  His  initial  injection  varies 
from  15-25  c.c.  in  adults,  and  is  proportionally  diminished  in  children. 
This  injection  is  not  as  a  rule  repeated  under  twenty-four  hours,  and 
often  at  a  longer  interval.  Sophian  has  drawn  up  a  table  of  dosage 
for  serum  according  to  age.  This  author's  wide  experience  and  the 
methods  of  precision,  which  he  has  applied  to  the  solution  of  the 
question  of  dosage,  entitle  his  decisions  to  the  greatest  consideration. 
The  results  at  which  he  has  arrived  are  given  below. 


Age 

Dose 

Max. 

1-5    years 

3-12  c.c. 

12  CO. 

6-10      „ 

5-15  c.c. 

15  c.c. 

10-15      „ 

10-20  CO. 

20  o.c 

15-20      „ 

15-25  c.c. 

30  c.c 

20  years  and  over 

20-30  c.c. 

40  c.c. 

viij  Treatment  81 

Apart  from  other  considerations,  it  must  be  borne  in  mind  that 
these  doses  are  entirely  dependent  on  the  previous  removal  of  an 
appreciably  larger  quantity  of  fluid  from  the  spinal  canal.  With 
regard  to  the  frequency  with  which  the  injections  should  be  continued, 
both  Netter  and  Sophian  consider  that  they  should  be  repeated  daily 
so  long  as  the  indications  for  the  treatment  are  present.  In  their 
opinion  the  essential  guide  for  the  abandonment  or  repetition  of  the 
injections  is  afforded  by  the  bacteriological  characteristics  of  the 
cerebro-spinal  fluid.  The  indications  for  the  suspension  of  treatment 
are  marked  diminution  or  disappearance  of  the  meningococci,  the  few 
which  may  remain  staining  badly  and  she\^ing  involution  forms,  coupled 
with  more  or  less  complete  failure  to  grow  in  culture.  These  scanty 
organisms  are  all  found  to  be  intracellular.  The  presence  of  extra- 
cellular organisms  they  hold  to  be  a  strong  indication  for  the  continuation 
of  treatment,  as  is  also  the  growth  of  a  vigorous  culture.  Netter  insists 
on  the  possibly  misleading  nature  of  clinical  symptoms,  and  holds  it 
necessary  to  verify  the  condition  of  the  patient  by  an  occasional 
diagnostic  puncture.  It  will  thus  be  seen  that  an  essential  of  serum 
treatment  is  that  it  should  be  methodically  conducted  under  bacterio- 
logical guidance.  A  single  injection  cannot  be  considered  to  be 
treatment. 

Should  it  be  determined  to  rely  upon  lumbar  puncture  solely,  the 
first  essential  point  is  that  it  should  be  practised  methodically.  During 
the  acute  stage  a  daily  lumbar  puncture  is  frequently  necessary.  For 
the  efficient  performance  of  lumbar  puncture,  so  as  to  ensure  a  com- 
plete evacuation  of  the  excess  of  cerebro-spinal  fluid,  an  anaesthetic  is 
necessary.  In  our  experience,  the  daily  administration  of  an  anaesthetic 
for  several  successive  days  has  never  produced  any  ill  effect.  A  further 
point  is  that  as  much  fluid  as  possible  should  be  evacuated,  the  fluid 
being  allowed  to  run  until  the  rate  of  flow  amounts  to  one  drop  in  every 
two  or  three  seconds.  In  the  course  of  .300  successive  punctures  in  this 
disease  we  have  seen  no  signs  of  collapse  follow  the  evacuation  of  large 
quantities  of  fluid,  even  on  removing  as  much  as  three  ounces.  With 
due  precautions  the  danger  of  sepsis  may  be  disregarded.  The  only 
contamination  on  culture  that  we  have  met  with  is  staphylococcus 
albus,  this  is  not  infrequent,  and  is  derived  from  the  skin.  Severe 
headache  is  a  sure  indication  for  puncture  and  may  often  be  a  warning 
of  impending  hydrocephalus.  The  amount  of  fluid  obtained,  coupled 
with  the  increased  pressure  with  which  it  funs,  will  confirm  the 
rehabihty    of    this    warning    symptom.     When    the    acute    symptoms 

F.  &G  6 


82  Treatment  [ch. 

demanding  daily  lumbar  puncture  have  subsided,  resort  to  this  operation 
may  frequently  be  necessary  in  the  later  stages  of  the  disease.  A  sudden 
lapse  into  an  adynamic  state  calls  for  immediate  puncture,  which  should 
be  repeated  daily  until  the  condition  has  passed  off.  Persistent  fever 
even  without  cerebral  symptoms  calls  for  drainage  of  the  theca.  An 
apyrexial  period,  generally  of  some  days,  will  follow  the  evacuations  of 
the  fluid.  Slight  attacks  of  fever,  accompanied  by  headache  and  possibly 
vomiting  during  convalescence,  will  be  cut  short  by  timely  interference. 
We  have  personally  relied  more  on  clinical  symptoms  as  guides  for 
lumbar  puncture  than  upon  the  bacteriological  condition  of  the  cerebro- 
spinal fluid.  In  our  experience,  the  examination  of  film  preparations 
do  not  provide  such  great  differences  as  to  enable  them  to  act  as 
a  guide  in  those  cases  in  which  the  advisability  of  puncture  is  doubtful. 
In  almost  all  cases  clinically  doubtful  the  number  of  meningococci  in 
the  film  is  scanty,  and  may  require  considerable  search  to  be  identified 
with  certainty.  The  results  of  culture  may  also  be  misleading,  for  the 
ease  with  which  an  organism  can  be  grown,  varies  very  greatly  in  different 
cases,  so  that  the  absence  or  feeble  character  of  growth  in  culture  does 
not  negative  the  necessity  for  puncture.  In  some  of  our  hydrocephalic 
cases  the  fluid  obtained  has  been  negative  as  regards  growth  and  no 
cocci  have  been  found  in  film,  yet  the  necessity  for  the  relief  of  intra- 
cranial pressure  has  been  most  obvious  on  cUnical  grounds.  Although 
the  rules  laid  down  by  Netter  and  Sophian  are  equally  apphcable  to 
treatment  by  lumbar  puncture  alone,  and  should  always  be  followed, 
we  nevertheless  hold  that  clinical  indications  must  also  be  carefully 
watched.  In  that  group  of  cases,  in  which  the  rise  of  intracranial 
pressure  is  leading  on  to  the  early  stages  of  hydrocephalus,  the 
bacteriological  changes  of  the  cerebro-spinal  fluid  may  be  very  shght, 
meningococci  being  almost  absent.  The  only  guides  for  the  prevention 
of  the  establishment  of  this  condition  are  clinical.  It  is  precisely  in 
such  a  condition  that  repeated  lumbar  puncture  is  necessary.  The 
frequency  of  lumbar  puncture  should  therefore  be  guided  both  by 
clinical  symptoms  and  bacteriological  results. 

The  danger  from  a  too  rapid  lowering  of  cerebro-spinal  pressure  may 
be  disregarded.  Clinically  we  have  never  met  with  any  symptoms  of 
sudden  shock  or  collapse  due  to  this  cause.  No  arbitrary  limits  should 
be  placed  on  the  number  of  punctures  in  any  particular  case.  In  a  man 
under  our  care,  in  whom  the  dominant  symptom  was  intense  headache, 
and  whose  illness  ran  a  very  prolonged  course  of  over  two  months, 
thirty-two  punctures  in  all  were  performed,  the  last  taking  place  on  the 


vii]  Treatment  83 

60th  day  of  disease.  Clinically  his  condition  was  such  as  to  give  rise  to 
the  fear  that  he  was  developing  hydrocephalus,  and  on  this  hypothesis 
treatment  was  rigorously  persevered  with.  This  patient  finally  recovered 
completely,  and  when  last  heard  of  was  doing  duty  with  a  cavalry 
regiment.  With  regard  to  the  remote  after-effects  of  repeated  puncture, 
it  is  an  extremely  difficult  matter  to  differentiate  them  from  the  sequelae 
of  the  disease  itself.  Cases  running  a  prolonged  course  suffer  con- 
siderably from  severe  pain  and  weakness  in  the  back  and  legs,  and  for 
a  long  time  experience  difficulty  in  walking.  That  this  may  be  a  sequela 
of  the  disease  and  not  of  pimcture  is  proved  by  the  history  of  one  of 
our  cases.  This  patient  was  punctured  once  before  being  sent  to  us 
and  the  diagnosis  thus  confirmed.  This  puncture  was  attended  by 
somewhat  alarming  collapse.  On  admission  he  was  found  to  present 
well-marked  auricular  fibrillation,  with  definite  cardiac  symptoms,  of 
which  sleeplessness  was  the  predominant  feature.  Therefore  no  further 
puncture  was  deemed  advisable,  so  long  as  appreciable  progress  was  being 
made.  The  disease  consequently  ran  a  protracted  course,  the  man  not 
being  free  from  symptoms  for  forty  days.  During  convalescence  he 
exhibited  the  before-mentioned  symptom  of  pain  in  the  back  in  a  more 
marked  degree  than  patients  who  had  received  a  dozen  or  more  punctures. 
These  symptoms,  whether  dependent  on  the  disease  or  on  lumbar 
puncture,  ultimately  completely  disappear.  In  any  case,  they  are  not  of 
sufficient  moment  to  occasion  ground  for  hesitation  in  performing  lumbar 
puncture  an  indefinite  number  of  times,  when  thought  advisable.  The 
passage  of  a  sterile  needle  through  the  muscles  and  the  Hgamentum 
subflavum  appears  to  cause  almost  no  reaction.  In  our  experience  there 
has  never  been  any  evidence  of  inflammatory  reaction  about  the  line  of 
puncture.  Repeated  puncture  over  the  small  area  available  between 
the  4th  and  5th  lumbar  vertebrae  causes  no  alteration  of  structure 
which  can  be  felt  on  introducing  the  needle.  The  thirtieth  puncture 
can  be  performed  with  as  great  ease  as  the  first. 

We  have  already  repeatedly  insisted  on  the  view  held  by  us  that 
the  essence  of  all  treatment  of  cerebro-spinal  fever  lies  in  the  adequate 
drainage  of  the  sub-arachnoid  space.  Other  methods  of  treatment 
have  also  been  employed  which  require  a  brief  notice.  The  subcutaneous 
injection  of  serum  has  already  been  referred  to,  and  its  want  of  success 
indicated.  Serum  has  also  been  introduced  intravenously  and  intra- 
muscularly mth  equally  disappointing  results. 

Another  method  of  influencing  the  disease,  based  on  bacteriological 
grounds,  consists  in  the  administration  of  vaccines.     With  the  extensive 


84  Treatment  [CH. 

trial  of  vaccines  in  many  diseases  of  known  bacterial  origin,  attempts 
were  naturally  made  to  influence  epidemic  meningitis  by  these  methods. 
During  the  epidemic  of  1915,  vaccines  were  employed  to  a  considerable 
extent.  In  a  large  proportion  of  the  cases  other  methods  of  treatment, 
such  as  the  administration  of  serum  or  simple  lumbar  puncture,  were 
concurrently  employed.  Under  these  circumstances,  it  is  impossible  to 
assign  a  relative  value  to  either  form  of  treatment.  Rolleston  states 
that  in  the  Royal  Navy  a  few  cases  were  treated  by  autogenous  vaccines 
with  a  mortaUty  of  25  per  cent.  Horder  quotes  a  case  of  Dr  A.  E. 
Garrod's,  in  which  vaccine  given  on  the  39th,  41st,  43rd  and  45th  day 
was  succeeded  by  a  rapid  fall  of  temperature.  Improvement  was 
maintained  until  the  59th  day,  when  a  relapse  took  place,  vaccine  was 
again  injected  with  the  result  that  the  temperature  fell  permanently. 
That  treatment  by  vaccines  alone,  to  the  exclusion  of  more  direct  and 
energetic  methods,  would  ever  be  justifiable,  appears  most  improbable. 
How  far  vaccines  may  be  helpful  in  the  later  stages  of  a  persistently 
febrile  case  remains  to  be  determined.  Up  to  the  present,  adequate 
clinical  evidence  for  the  solution  of  this  question  is  lacking.  Another 
aspect  of  vaccine  treatment  is  the  advisability  of  the  routine  use  of 
vaccination  as  a  protective  measure  during  an  epidemic.  Sophian 
has  demonstrated  anti-bodies  in  the  blood  of  persons  who  have  been 
injected  with  vaccines.  The  wisdom  of  a  general  adoption  of  such 
a  procedure  would  appear  doubtful.  A  vaccinated  person  would  be 
more,  rather  than  less,  susceptible  during  the  negative  phase.  Bearing 
in  mind  the  method  of  spread  of  the  disease,  very  extensive  observations 
would  be  necessary  before  a  judgment  could  be  arrived  at  in  the  matter. 
Attempts  have  also  been  made  to  destroy  the  infection  by  the 
introduction  of  chemical  poisons  into  the  blood  stream.  Arguing  from 
the  analogy  of  its  success  against  the  spirochaete  and  in  trypanoso- 
miasis, soamin  has  been  tried.  Soamin  was  first  used  in  the  treatment 
of  cerebro-spinal  fever  by  the  medical  officers  of  the  troops  quartered  in 
East  Africa.  Shircore  and  Ross,  in  an  epidemic  in  British  East  Africa, 
claim  to  have  met  with  considerable  success  from  its  use.  Their 
mortality,  however,  was  59  per  cent. ;  by  excluding  cases  dying  under 
60  hours  after  coming  under  observation,  they  claim  a  mortality  of 
37  per  cent.  As  such  an  exclusion  would  eliminate  all  cases  of  the 
acute  fatal  type,  the  only  figure  to  argue  from  is  the  complete  mortality. 
On  this  basis  their  mortality  is  higher  than  that  of  lumbar  pimcture 
with  or  without  serum,  and  only  slightly  lower  than  that  of  the  older 
epidemics.     In  the  epidemic  of  1915,  Rolleston  states  that  in  the  Royal 


vii]  Treatment  85 

Navy  27  cases  were  treated  with  soamin,  with  a  percentage  mortality 
of  33.  In  contrast  with  this,  18  cases  treated  with  soamin  and  serum 
combined  gave  a  mortahty  of  61  per  cent.  This  gives  a  mortality  of 
44  per  cent,  for  all  cases  in  which  soamin  was  given.  A  consideration 
of  these  two  sets  of  statistics  hardly  warrants  the  conchision  that  the 
efficacy  of  soamin  is  proved,  though  the  figures  are  lower  than  those  when 
neither  lumbar  puncture  nor  serum  has  been  employed.  Soamin  is 
usually  given  intramuscularly.  Five  grains  are  given  on  the  first 
two  days,  and  three  grains  on  the  fourth.  Optic  atrophy,  which  is 
an  occasional  effect  of  the  use  of  soamin,  does  not  appear  to  have  been 
reported  as  attending  its  use  in  this  connection.  Hexamine,  which  has 
been  suggested  as  an  alternative,  is  regarded  by  Rolleston  as  inert. 

Whatever  special  methods  are  adopted,  they  must  be  supplemented 
by  careful  attention  to  general  treatment.  In  the  case  of  hospital 
patients,  the  provision  of  a  special  ward  is  of  the  greatest  value.  The 
whole  arrangements  for  treatment  and  nursing  are  thus  more  efficiently 
carried  out.  Wherever  possible  the  ward  or  institution  for  treatment 
should  be  in  proximity  to  the  bacteriological  laboratory,  in  order  that 
immediate  examination  of  swabs  and  puncture  fluids  can  be  carried 
out.  In  our  experience  the  difficulties  attending  the  transport  of 
patients  were  slight,  and  the  danger  negligible.  Upwards  of  seventy 
cases  or  suspected  cases  were  brought  into  our  ward  by  motor  ambulance 
during  the  epidemic  of  1915.  The  distances  to  be  traversed  were  often 
considerable,  amounting  in  some  cases  to  sixty  miles ;  but  even  in  acute 
cases,  no  ill  effect  was  observed.  The  freest  possible  ventilation  should 
be  maintained,  both  night  and  day,  in  all  weathers.  The  open  air 
method  of  treatment  universal  in  the  First  Eastern  General  Hospital 
may  have  contributed  to  the  comparatively  favourable  results  obtained. 
Strict  precautions  should  be  taken  as  regards  the  disinfection  of  all 
discharges,  notably  the  nasal  and  oral  secretions.  The  mouth  should  be 
kept  as  clean  as  possible  by  swabbing  with  a  mild  antiseptic.  All  hnen 
and  bedclothes  should  be  kept  apart  from  those  of  other  patients  and 
plunged  into  strong  antiseptics.  All  nurses  and  convalescent  patients 
should  gargle  and  irrigate  the  nose  with  a  solution  of  1  part  permanganate 
of  potash  in  2000  parts  of  a  1-5  per  cent,  solution  of  sodium  sulphate. 
The  prevention  of  bed  sores,  especially  in  hydrocephalic  cases,  calls 
for  considerable  care.  Points  of  pressure,  such  as  the  trochanter  and 
points  of  the  shoulders,  should  be  attended  to.  In  the  latter  class  of 
case,  particular  attention  should  be  paid  to  the  position  of  the  patient, 
since  every  movement  is  apt  to  be  extremely  painful.     A  careful  watch 


86  ~        Treatment  [ch. 

should  be  kept  on  the  bladder.  Any  distension  or  overflow  incon- 
tinence should  at  once  be  met  by  the  use  of  the  catheter. 

In  the  acute  stages  the  nourishment  should  be  restricted  to  fluids, 
milk,  beef-tea,  and  beaten-up  eggs.  When  vomiting  is  an  urgent 
symptom,  whey  will  be  found  to  be  best  supported.  When  the  patient 
is  unable  to  swallow,  recourse  should  be  had  to  rectal  feeding, 
peptonized  milk  with  eggs  and  brandy  may  be  administered  four- 
hourly.  Should  this  method  present  any  difficulty,  this  may  be 
overcome  by  nasal  feeding.  Four  feeds  a  day  of  peptonized  milk  and 
egg  with  brandy  may  be  administered  by  the  nasal  tube.  As  the 
acute  symptoms  pass  off,  a  full  dietary  is  usually  well  borne,  even 
when  some  fever  still  persists.  The  use  of  stimulants  should  be  confined 
to  the  acute  cases.  During  the  earlier  days,  when  the  patient  is  either 
in  a  state  of  stupor  or  delirium,  two  to  three  ounces  of  brandy  should 
be  given  at  intervals  in  divided  doses  during  the  24  hours.  This  amount 
should  be  increased  if  signs  of  cardiac  distress  appear.  Stimulants  of 
all  kinds  are  best  avoided  after  the  acute  stage  has  passed,  and  during 
convalescence. 

No  drug  can  be  said  to  exert  any  specific  action  in  this  disease. 
It  is  an  open  question  whether  any  drug  is  of  value  except  for  the  relief 
of  symptoms.  Urotropin  was  regarded  as  likely  to  exert  a  beneficial 
influence,  by  reason  of  the  fact  that  it  had  been  proved  to  be  secreted 
into  the  cerebro-spinal  fluid.  The  value  attached  by  surgeons  to  a 
preliminary  course  of  urotropin  before  a  cerebral  operation  formed 
another  reason  in  its  favour.  In  our  own  experience,  it  has  undoubtedly 
had  a  markedly  beneficial  effect  in  cases  of  disseminated  sclerosis. 
Fifteen  consecutive  cases  of  cerebro-spinal  fever  in  our  ward  were 
treated  with  urotropin  and  the  following  fifteen  without.  As  far  as 
a  judgment  could  be  arrived  at,  a  very  difficult  matter  in  this  disease, 
the  drug  seemed  to  be  entirely  inert.  Iodide  of  potassium  and  mercury 
have  traditionally  been  employed  in  all  forms  of  meningitis.  The 
analogy  of  their  success  in  cerebral  syphihs,  and  the  temporary  im- 
provement following  their  use  in  cases  of  cerebral  tumour,  warranted 
their  being  given  a  trial.  From  a  pathological  point  of  view,  it  is 
difficult  to  see  how  they  could  act  beneficially;  in  practice  they  have 
failed  of  success. 

Of  special  symptoms,  the  agonizing  headache,  met  with  both  in  the 
early  stage  and  in  hydrocephaUc  conditions,  can  be  alleviated  only  by 
the  use  of  morphia  hypodermically.  A  somewhat  curious  feature  of 
cerebro-spinal  fever  is  that,  when  the  headache  ceases,  no  craving  for 


vii]  Treatment  87 

morphia  remains.  Even  when  the  patient  calls  out  for  morphia  on 
accoimt  of  the  severity  of  his  headache,  no  fear  need  be  entertained  of 
the  formation  of  a  drug  habit.  In  our  experience,  no  difficulty  was  ever 
found  in  discontinuing  the  drug.  No  hesitation  need  be  felt  in  having 
recourse  to  morphia  when  the  pain  is  severe.  A  severe  headache,  met 
with  at  any  stage,  is  an  indication  for  lumbar  puncture.  Pain  milder  in 
degree  is  reheved  by  aspirin,  phenacetin  or  antipyrin.  An  ice-bag  to 
the  head  is  a  useful  auxiliary  measure.  Leeches  to  the  temples  or 
mastoid  give  considerable  relief.  Insomnia  is  often  a  marked  feature. 
For  its  reHef  bromidia  is,  in  our  experience,  the  most  efficient  hypnotic, 
it  may  be  given  in  drachm  doses,  and  repeated  in  4  or  5  hours  if 
necessary.  Vomiting  is  rarely  a  troublesome  symptom  for  more  than 
24  hours.  Dilute  hydrocyanic  acid  with  bismuth  and  a  diet  of  whey 
or  complete  starvation  will  give  relief.  Should  the  urgency  remain 
unabated,  morphia  must  be  given. 

In  the  acute  stages,  prostration  must  be  guarded  against  from  the 
outset.  In  all  acute  cases  rectal  injections  of  normal  saline  should  be 
given.  The  pulse  and  general  appearance  of  the  patient  will  serve  as 
a  guide  to  the  frequency  of  their  repetition,  which  may  take  place 
every  12  to  8  hours.  In  comatose  cases  a  pint  of  normal  saline  solution 
should  be  slowly  transfused  under  the  skin  twice  in  the  24  hours.  In 
these  cases  hypodermic  injection  of  strychnine  or  Curschmann's  solution 
should  be  given  two  or  three  times  in  the  24  hours. 

When  arthritis  appears  as  a  complication,  warm  applications  should 
be  applied  to  the  affected  joint,  combined,  if  necessary,  with  the  use 
of  a  light  sphnt.  If  the  joint  remain  tense,  aspiration  should  be 
employed.  The  local  injection  of  serum  has  been  successfully  employed 
by  Flexner  and  others. 

With  the  disappearance  of  cerebral  symptoms  in  chronic  cases  the 
gain  in  flesh  is  remarkably  rapid.  In  our  experience,  no  condition  of 
nutrition  has  arisen  calling  for  any  treatment  beyond  fresh  air  and 
abundant  food.  As  has  been  before  insisted  upon,  palsies  of  special 
nerves  or  loss  of  power  in  a  limb  tend  almost  invariably  to  spontaneous 
recovery.  Passive  movements  to  the  joints  should  be  employed  to 
prevent  the  formation  of  adhesions.  The  stiffness  of  the  back  may  be 
treated  by  gentle  massage. 

When  hydrocephalus  has  become  estabhshed  and  all  attempts  at 
securing  drainage  by  means  of  lumbar  puncture  have  proved  fruitless, 
the  question  of  operative  interference  may  be  considered.  Surgical 
procedures  of  many  kinds  have  been  devised  and  practised  in  the  hope 


§8  Treatment  [ch. 

of  relieving  a  condition  which  otherwise  would  appear  to  be  necessarily 
fatal.  Hitherto  the  success  attending  these  operations  in  cases  of 
posterior  basic  and  tuberculous  meningitis  in  children  has  not  been 
such  as  to  encourage  any  sanguine  anticipation  of  success.  On  the  other 
hand  chnical  experience  shews  that,  if  the  tension  of  the  cerebro-spinal 
fluid  is  not  reheved,  the  case  can  have  only  one  ending.  From  the  nature 
of  the  disease  and  the  dangers  incidental  to  an  operation,  surgical 
procedures  are  only  as  a  rule  undertaken  in  the  last  resort.  In  infants, 
where  the  fontanelle  is  still  open,  the  operation  of  tapping  the  ventricles 
has  occasionally  been  followed  by  a  successful  residt.  The  dangers 
attending  this  surgical  procedure  are  not  so  great  as  is  the  case  in  the 
adult,  death  from  shock  is  an  uncommon  event  and  the  danger  of  sepsis 
is  practically  negUgible.  Should  this  operation  be  decided  upon  the 
method  is  as  follows.  The  spot  chosen  for  the  entry  of  the  needle  is 
the  lateral  angle  of  the  anterior  fontanelle  one  inch  from  the  middle 
line.  The  needle  is  directed  downwards  and  towards  the  middle  Une 
for  a  distance  varying  from  an  inch  to  an  inch  and  a  quarter.  The 
needle  must  be  gently  pushed  onwards  until  fluid  is  observed  to  flow, 
the  precise  depth  at  which  the  fluid  will  be  reached  varying  with  the 
age  of  the  child  and  the  degree  of  dilatation  of  the  ventricles. 
Should  it  be  determined  to  introduce  serum,  this  must  be  accomplished 
with  the  greatest  caution.  The  amount  of  serum  injected  must  be  very 
definitely  less  than  the  quantity  of  fluid  removed.  The  greatest 
watchfulness  must  be  exercised  in  ensuring  that  the  injection  is  made 
directly  into  the  cavity  of  the  ventricle  and  not  into  the  cerebral  tissue, 
as  the  serum  may  exercise  an  irritant  effect  on  the  latter.  Some  cases 
treated  by  means  of  ventricular  puncture  undoubtedly  recover:  the 
essential  obstacle  to  greater  success  Ues  in  the  diverse  sites  of  the 
obstruction  to  the  circulation  of  cerebro-spinal  fluid.  In  the  adult  the 
risk  of  surgical  interference  is  increased,  as  trephining  must  necessarily 
precede  ventricular  puncture.  Moreover,  in  cases  of  increased  intra- 
cranial tension,  sudden  death  during  the  administration  of  an  anaesthetic 
which  of  itself  increases  the  pressure,  is  a  possibility  to  be  borne  in  mind. 
At  the  same  time  the  condition  of  the  patient  affords  no  hope 
of  cure  from  expectant  treatment  if  lumbar  puncture  has  failed  to 
relieve  pressure.  Under  such  circumstances  the  risks  attending  the 
operation  may  be  undertaken. 

In  order  to  drain  the  lateral  ventricle  two  routes  have  been  employed 
which  are  associated  with  the  names  of  Keen  and  Kocher  respectively. 
A  circle  of  bone  must  be  removed  by  a  half  inch  trephine,  the  centre 


vii]  Treatment  89 

of  which  corresponds  with  the  point  at  which  it  is  proposed  to  insert 
the  needle.  Keen  thus  describes  his  method.  The  exploring  needle  is 
introduced  through  the  cortex  at  a  point  3  centimetres  (or  \\  inches) 
behind,  and  the  same  distance  above,  the  level  of  the  centre  of  the 
external  auditory  meatus,  and  directed  towards  the  top  of  the  auricle 
of  the  opposite  side.  The  ventricle  is  found  at  a  depth  of  5  centimetres 
(or  2  inches)  where  it  is  gi'ving  off  its  descending  and  posterior  cornua. 
Lieut.  Col.  H.  A.  Ballance,  to  whom  we  are  indebted  for  information  as 
regards  the  operative  aspect  of  hydrocephalus,  favours  the  insertion  of 
a  fine  drainage  tube,  should  a  more  lasting  effect  than  that  produced  by 
tapping  be  desired.  For  this  proceduje  the  dura  mater  is  first  incised 
and  either  a  grooved  director  or  sinus  forceps  passed  through  the 
cerebral  tissue  in  the  direction  already  speciiied,  care  being  taken  to 
avoid  a  cortical  vein ;  a  flow  of  fluid  by  the  side  of  the  instrument  will 
indicate  that  the  ventricle  has  been  reached.  A  drainage  tube  is  then 
introduced  and  its  end  sutured  to  the  free  edge  of  the  dura  mater. 
Should  Kocher's  method  be  employed,  the  instrument  is  introduced 
1  inch  from  the  middle  line,  and  \\  inches  anterior  to  the  central  fissure. 
This  point  lies  a  short  distance  in  front  of  the  bregma.  The  instrument 
should  be  directed  downwards  and  slightly  backwards,  to  a  depth  of 
\\  to  2  inches,  when  the  ventricle  will  be  reached.  A  further  and  very 
efficient  procedure  is  to  drain  the  sub-arachnoid  space  from  the  posterior 
fossa.  A  trephine  opening  is  made  over  one  cerebellar  hemisphere  and 
enlarged  to  a  suitable  extent.  After  incising  the  dura  mater  the 
cerebellar  hemisphere  is  lifted  up.  This  manceuvre  will  separate  any 
adhesions  between  the  cerebellum  and  the  roof  of  the  fourth  ventricle, 
which  are  causing  obstruction  to  the  flow  of  cerebro-spinal  fluid.  An 
immediate  gush  of  fluid  takes  place,  and  subsequent  drainage  may  be 
secured  by  the  insertion  of  a  fine  tube. 

Temporary  improvement  has  not  infrequently  followed  one  or  other 
of  these  operations  when  performed  for  internal  hydrocephalus  what- 
ever may  be  its  cause,  but  permanent  cure  is  an  event  of  extreme 
rarity.  A  study  of  the  morbid  lesions  associated  with  hydrocephalus 
in  cerebro-spinal  fever  reveals  the  fact  already  stated,  that  the  drainage 
effected  by  any  particular  operation  may  prove  to  be  only  partial.  On 
the  other  hand  it  must  be  borne  in  mind  that  the  danger  at  this  stage 
is  chiefly  due  to  a  physical  cause,  and  that  the  initial  infective  processes 
have  largely  ceased.  There  is,  therefore,  good  reason  to  hope  that 
ventricular  drainage  may  be  more  successful  in  this  disease  than  in  those 
for  which  this  procedure  has  hitherto  been  mainly  employed. 


CHAPTER  VIII 

PATHOLOGY 

Nomenclature.  The  meningococcus  of  Weichselbaum,  the  cause  of 
epidemic  meningitis,  including  posterior  basic  meningitis.  Anatomy 
of  the  membranes  of  the  brain  and  cord.  The  circulation  of  the  cerebro- 
spinal fluid.  Post-mortem  appearances,  the  fulminating  type,  the 
acute  fatal  type,  site  of  the  infection,  sub-acute  type,  suppurative 
type,  chronic  type  with  hydrocephalus.  The  organism  of  posterior 
basic  meningitis,  path  of  infection.  The  reaction  of  the  body  to 
invasion,  leucocytosis,  serum  changes,  agglutination,  opsonic  index, 
complement  fixation,  bactericidal  properties. 

Cerebro-spinal  fever  is  a  specific  fever  in  which  the  whole  brunt  of 
the  infection  falls  upon  the  central  nervous  system  and  its  coverings 
the  meninges ;  only  rarely  do  symptoms  arise  which  can  be  definitely 
related  to  infection  or  injury  of  other  organs.  Inasmuch  as  the  infective 
agent  attacks  primarily  and  almost  exclusively  the  membranes  of  the 
brain,  the  disease  is  a  true  meningitis.  Now  the  relationship  of  these 
membranes  to  the  brain  and  cord  is  such  that  all  forms  of  meningitis 
must  of  necessity  be  cerebro-spinal.  The  term  cerebro-spinal  meningitis, 
which  is  in  common  use,  is  therefore  redundant,  cumbersome  and 
unnecessary.  The  epidemic  nature  of  cerebro-spinal  fever  can  be 
denoted  sufficiently  accurately  by  the  synonym  epidemic  meningitis, 
which  we  propose  to  use  instead  of  the  very  compHcated  phrase  epidemic 
cerebro-spinal  meningitis. 

It  has  now  been  firmly  established  that  the  meningococcus  of 
Weichselbaum  is  the  causative  agent  in  by  far  the  greater  number  of 
epidemic  outbreaks  of  meningitis.  It  is  therefore  permissible  to  identify 
the  terms  epidemic  meningitis,  or  cerebro-spinal  fever,  with  infections 
due  to  the  meningococcus  only. 

The  meningococcus  was  discovered  in  1887  by  Weichselbaum,  who 
found  a  gram-negative  diplococcus  present  in  the  cerebro-spinal  fluid 
in  cases  from  an  epidemic  at  Vienna.  By  the  use  of  agar,  with  2  per 
cent,  gelatine  added,  he  was  able  to  cultivate  the  organism,  though 
it  was  too  delicate  to  grow  on  ordinary  laboratory  media. 


CH.  viii]  Pathology  91 

Tliis  work  of  Weichselbaum's  was  thrown  into  doubt  and  considerably 
confused  by  the  work  of  Jaeger,  Heubner  and  their  followers,  who 
maintained  that  a  gram-positive  coccus  could  be  isolated  from  the 
cerebro-spinal  fluid  in  many  epidemics.  Further  investigations  by 
observers  all  over  the  world  have,  however,  fully  substantiated 
Weichselbaum's  original  statements,  and  it  is  now  universally  accepted 
that  the  meningococcus  described  by  liim  is  the  cause  of  epidemic 
meningitis. 

It  is  probable  that  the  meningococcus  is  always  present  to  a  greater 
or  less  extent  in  countries  where  epidemics  occur;  just  as  is  the  case 
with  diphtheria.  The  meningococcus  is  carried  in  the  throat  of  normal 
individuals,  but  under  modern  hygienic  conditions  usually  only  attacks 
infants  under  the  age  of  two.  In  England  there  are  every  year  a  certain 
number  of  cases  of  this  form  of  the  disease,  which  are  usually  extremely 
chronic,  often  lasting  as  long  as  nine  months.  They  thus  indicate  the 
comparatively  low  virulence  of  the  organism  imder  normal  conditions. 
The  first  description  of  this  disease  of  infants  was  given  by  Gee  and 
Barlow,  it  has  therefore  been  called  "Gee  and  Barlow's  Disease,"  and 
also,  owing  to  the  distribution  of  the  lesions  at  the  base  of  the  brain, 
"Posterior  Basic  Meningitis."  The  identification  in  this  disease  of  a 
coccus  similar  to  the  meningococcus  is  due  to  Still  in  1898.  In  studying 
the  pathology  of  cerebro-spinal  fever,  these  cases  must  be  included,  as 
their  etiology  is  essentially  the  same ;  but  their  occurrence  is  so  sporadic 
and  comparatively  infrequent  that  they  can  hardly  be  included  in  the 
term  Epidemic  Meningitis.  To  put  the  matter  in  another  way; 
posterior  basic  meningitis  is  a  mild  sporadic  form  of  epidemic  meningitis. 
Both  are  due  to  the  same  infective  agent,  the  meningococcus  of 
Weichselbaum. 

The  differential  diagnosis  of  the  disease  by  clinical  methods  is  often 
a  matter  of  extreme  difficulty,  as  has  already  been  insisted  upon;  in 
fact  a  diagnosis  between  an  acute  cerebro-spinal  infection  by  the 
meningococcus,  and  a  similar  infection  by  some  other  organism,  is 
practically  impossible  without  bacteriological  aid.  The  diagnosis  is 
only  firmly  established  when  the  meningococcus  has  been  grown  in 
pure  culture  from  the  cerebro-spinal  fluid. 

The  cultural  characteristics  of  the  organism  will  be  discussed  in  the 
final  chapter.  It  is  a  diplococcus  which,  when  first  obtained  from  the 
body,  is  always  gram-negative  and  is  almost  exclusively  intracellular, 
being  found  in  the  cytoplasm  of  polymorphonuclear  leucocytes.  It  can 
practically  always  be  found  in  the  cerebro-spinal  fluid  of  those  suffering 


92  Pathology  [CH. 

from  the  disease,  and  also  in  the  secretion  of  the  posterior  pharynx  in 
about  25  per  cent,  of  cases.  Certain  authors  claim  to  have  recovered 
the  organism  with  frequency  from  the  urine,  and  also  not  uncommonly 
from  the  blood;  they  therefore  maintain  that  the  disease  is  in  its 
initial  stages  a  septicaemia.  The  evidence  for  this  is,  however,  con- 
flicting, and  the  question  will  be  further  discussed  in  the  next  chapter. 

In  order  to  describe  more  easily  the  pathological  conditions  found, 
it  will  be  convenient  to  recall  the  anatomical  arrangements  and  relation- 
ships of  the  membranes  of  the  brain.  The  brain  lies  to  a  great  extent 
free  inside  the  skull  cavity,  being  kept  in  position  by  the  falx  cerebri 
and  the  tentorium  cerebelli;  its  actual  attachments  consist  only  of 
the  out-going  nerves  and  the  vessels  which  supply  blood  to  the  pia 
mater.  The  cavity,  in  which  the  brain  lies,  is  a  serous  sac  completely 
lined  by  the  arachnoid  membrane.  At  any  point  on  the  vertex  there 
are  therefore  four  layers  investing  the  brain;  the  dense  dura  mater 
lining  the  skull,  the  parietal  layer  of  the  arachnoid  fused  with  the 
dura  mater  and  forming  its  inner  lining,  the  visceral  layer  of  the 
arachnoid,  and  the  pia  mater.  When  the  brain  is  removed  from  the 
skull,  the  dura  mater  and  parietal  arachnoid  have  been  cut  through; 
but  the  organ  is  still  invested  by  the  visceral  layer  of  the  arachnoid 
and  the  dura  m#ter.  At  one  point  only  is  difficulty  experienced  in 
freeing  these  two  pairs  of  membranes  from  each  other,  namely  in  the 
vertical  region  along  the  longitudinal  sinus.  This  difficult}^  is  due  to 
the  presence  of  the  pacchionian  bodies,  which  consist  of  little  knobs 
formed  by  the  invagination  of  the  visceral  arachnoid  through  the 
parietal  arachnoid  and  dura  into  the  longitudinal  sinus.  The  cavity  of 
these  bodies  is  thus  continuous  with  the  space  lying  between  the  visceral 
arachnoid  and  the  pia  mater,  known  as  the  sub-arachnoid  space :  they 
protrude  into  the  longitudinal  sinus,  being  covered  with  a  comparatively 
thin  \a,yQT.  of  the  dura.  There  is  evidence  that  a  fairly  free  exchange 
takes  place  between  fluid  in  the  sub-arachnoid  space  and  the  blood  in  the 
longitudinal  vein,  in  which  the  pacchionian  bodies  probably  play  a  part. 

The  pia  mater  very  closely  invests  the  brain,  dipping  down  into  the 
sulci  and  supplying  blood  vessels  to  its  substance.  The  visceral 
arachnoid  does  not  invest  the  brain  so  closely;  there  is  thus  a  space 
between  these  membranes,  which  is  known  as  the  sub-arachnoid  space. 
In  this  space  circulates  the  cerebro-spinal  fluid.  The  sub-arachnoid 
space  is  practically  a  potential  space,  where  it  lies  over  the  convolutions 
of  the  brain;  but,  where  the  visceral  arachnoid  passes  over  the  sulci, 
it  leaves  a  considerable  triangular  interval  between  itself  and  the  pia 


vin] 


Pathology 


93 


mater,  which  dips  down  on  either  side  of  the  sulcus,  so  that  the 
sub-arachnoid  space  is  here  of  some  size.  The  space  is  not  a  simple 
one  but  is  crossed  by  numerous  trabeculae  which  anchor  the  two 
membranes  together.  As  the  large  vessels  run  in  the  sulci,  there  is 
therefore  a  considerable  perivascular  space  formed  by  the  sub-arachnoid 
cavity. 

At  the  base  of  the  brain  the  arrangement  differs  considerably,  for 
the  visceral  arachnoid  becomes  in  places  even  more  widely  separated 
from  the  brain  and  pia  mater.  Certain  considerable  spaces  are  thus 
formed,  which  are  known  as  cisternae,  and  contain  normally  a  consider- 


Optic  chiasma 


Cisterna  interpedunciilai  ts 


Cisterna 
cerebello-medullari 
Fia.  1. 


able  quantity  of  cerebro-spinal  fluid.  The  arrangement  of  these 
cisternae  is  shewn  in  Fig.  1.  On  the  upper  surface  of  the  brain  the 
chief  cisterna  is  the  cisterna  magna,  or  cerebello-medullaris ;  it  forms 
a  cavity  lying  between  the  roof  of  the  fourth  ventricle  and  the  cerebellum. 
This  cavity  is  of-great  importance,  as  it  has  communication  with  the 
fourth  ventricle,  and  thus  with  the  internal  ventricles  of  the  brain, 
through  certain  openings  in  the  roof  of  the  ventricle  known  as  the 
foramina  of  Majendie  and  Luschka.  The  cisterna  magna  is  continuous 
caudally  with  the  sub-arachnoid  space  of  the  cord.  On  the  under 
surface  of  the  base  of  the  brain  two  large  cisternae  are  present.     The 


94  Pathology  [ch. 

anterior  covers  the  region  in  whicli  lies  the  circle  of  Mollis,  starting 
in  front  of  the  optic  chiasma  and  extending  back  to  the  pons; 
laterally  it  extends  to  the  temporal  lobes.  It  is  known  as  the  cisterna 
interpeduncularis  or  basalis.  Over  the  pons  the  visceral  arachnoid 
comes  to  lie  close  to  the  pia  mater,  but  behind  they  again  separate, 
where  the  pons  and  medulla  oblongata  join,  so  as  to  form  another  space 
known  as  the  cisterna  pontis.  The  cisterna  pontis  contains  the  basilar 
artery  and  becomes  continuous  caudally  with  the  sub-arachnoid  space 
of  the  cord.  The  sub-arachnoid  space  passes  forward  from  the  cisterna 
interpeduncularis  over  the  olfactory  lobes.  The  two  membranes, 
the  visceral  arachnoid  and  pia,  become  fused  with  the  sheaths  of  the 
olfactory  nerves  shortly  after  their  origin  from  the  olfactory  lobe, 
having  therefore  the  same  relationship  as  the  other  nerves  when  they 
leave  the  brain  and  cord.  The  relationship  of  the  dura  mater  is 
however  different  in  the  case  of  the  olfactory  nerves  from  that  of  other 
nerves.  In  the  latter  the  dura  also  becomes  fused  with  the  sheath  of 
the  nerve;  but  in  the  case  of  the  olfactory  nerves  it  does  not  join  the 
sheath  of  each  nerve,  but  passes  through  the  openings  in  the  cribriform 
plate  of  the  ethmoid  bone,  and  becomes  continuous  with  the  linings  of 
the  nasal  cavity.  The  fusing  of  the  visceral  arachnoid  and  the  sheath 
of  an  olfactory  filament  is  not  complete.  Andre  has  worked  out  in  the 
dog  and  the  rabbit  the  relationship  between  the  sub-arachnoid  space 
and  certain  channels  round  the  olfactory  nerves,  by  means  of  experi- 
mental injections  of  methylene  blue  and  Chinese  ink.  He  finds  that 
prolongations  of  the  sub-arachnoid  space  pass  downwards,  and  form  a 
network  aroimd  the  olfactory  filaments,  as  they  pass  through  the 
cribriform  plate.  There  are  also  other  prolongations  which  pass  through 
the  cribriform  plate  independently  of  the  olfactory  nerves.  A  successful 
injection  not  only  demonstrates  these  prolongations  but  also  colours 
the  mucous  membrane  of  the  nose  down  to  the  level  of  the  superior 
turbinated  bone  (Plate  V,  fig.  1).  He  concludes  that  direct  com- 
munication exists  between  the  prolongations  of  the  sub-arachnoid  and 
the  lymphatic  channels  of  this  portion  of  the  nose.  There  is  thus  free 
communication  between  the  sub-arachnoid  space  and  the  upper  regions 
of  the  nasal  mucous  membrane. 

The  membranes  of  the  cord  differ  in  arrangement  from  those  of  the 
greater  part  of  the  brain,  in  that  the  sub-arachnoid  space  is  much 
larger.  The  visceral  and  parietal  layers  of  the  arachnoid  lie  closely 
apposed  to  each  other,  while  the  visceral  arachnoid  and  the  pia  mater 
are    fairly    widely    separated.     When    the    dura    mater    and   parietal 


VIIl] 


Pathology 


95 


arachnoid,  which  form  the  theca  of  the  cord,  are  opened  and  reflected 
(Fig.  2),  the  visceral  arachnoid  is  seen  as  a 
thin  transparent  membrane  quite  loosely 
attached  to  the  underlying  pia  mater  and 
cord.  The  arrangement  is  therefore  as  is 
shewn  on  section  in  Fig.  3.  The  sub-dural 
or  arachnoid  cavity  between  the  two  layers 
of  the  arachnoid  is  only  a  potential  space; 
the  cord  lies  suspended  in  the  sub-arachnoid 
space,  which  is  filled  with  cerebro-spinal 
fluid.  As  the  cord  diminishes  caudally  and 
finally  is  only  represented  by  the  filuni  ter- 
minale  surrounded  by  the  Cauda  equina,  the 
sub-arachnoid  space  becomes  still  larger. 
The  spinal  sub-arachnoid  space  is  through- 
out divided  by  a  longitudinal  septum,  the 
sub-arachnoid  septum,  which  connects  the 
arachnoid  with  the  pia  mater  opposite  the 
posterior  fissure  of  the  cord.  Otherwise 
the  cavity  is  not  trabeculated.  The  sub- 
arachnoid cavity  in  the  region  of  the  4th 
and  5th  lumbar  vertebrae  is  thus  a  large 

space  filled  with  cerebro-spinal  fluid,  through  which  only  the  cauda  equina 
runs,  the  spinal  cord  terminating,  even  in  children,  not  lower  than  the 
3rd  lumbar  vertebra.  The  operation  of  lumbar  puncture  can  therefore  be 
safely  performed  in  this  region  without  fear  of  damage  to  the  cord :  there 


^  Subdural  cavity 


Pia  mater 
Arachnoid 
Dtira  mater' 


Subdural  cavity 


96  Pathology  [CH, 

is  also  usually  little  danger  of  seriously  injuring  the  nerves  forming  the 
Cauda  equina,  as  these  lie  practically  free  in  the  sub-arachnoid  space  and 
thus  slip  to  one  side  of  the  point  of  the  needle.  Another  anatomical 
point,  which  is  of  some  importance  when  performing  lumbar  puncture, 
is  the  presence  of  wide  veins  covering  the  posterior  surface  of  the  body 
of  the  vertebrae  in  this  region.  In  the  spinal  canal  the  dura  mater  is 
not  closely  apphed  to  the  bony  walls,  as  in  the  case  of  the  brain  and 
skull,  but  is  separated  by  a  considerable  amount  of  loose  areolar  tissue 
in  which  large  veins  run.  These  veins  are  especially  conspicuous  over 
that  part  of  the  wall  of  the  canal  which  is  formed  by  the  posterior 
aspect  of  the  bodies  of  the  vertebrae.  If  too  much  violence  is  used 
when  the  pimcture  needle  has  reached  the  sub-arachnoid  cavity,  the 
dura  mater  over  the  bodies  of  the  vertebrae  may  be  punctured  and 
considerable  bleeding  take  place;  the  cerebro-spinal  fluid  withdrawn 
will  then  be  much  bloodstained. 

The  very  free  communication  of  the  sub-arachnoid  cavity  of  the 
cord  with  the  sub-arachnoid  cisternae  and  spaces  of  the  brain  make  it 
clear  that  an  infection  of  the  membranes  of  the  brain  must  involve  the 
sub-arachnoid  space,  and  very  rapidly  become  diffused  throughout  both 
brain  and  cord.  It  is  therefore  reasonable  to  consider  that  every 
meningitis  is  cerebro-spinal  in  distribution. 

The  circulation  of  the  cerebro-spinal  fluid  is  at  present  not  completely 
understood.  The  evidence  however  points  to  the  choroid  plexuses  of 
the  various  ventricles  as  the  secretory  source.  The  path  of  absorption 
of  the  fluid  is  also  at  present  uncertain,  but  drugs  introduced  into  the 
sub-arachnoid  space  can  be  almost  immediately  recovered  from  the 
cerebral  venous  sinuses.  The  possible  paths  between  the  sub-arachnoid 
space  and  the  veins  are  many ;  the  cerebral  veins  run  directly  through 
the  sub-arachnoid  space  so  that  direct  absorption  by  them  is  very  likely. 
The  curious  structure  of  the  pacchionian  bodies  makes  it  probable 
that  these  bodies  are  also  concerned  in  the  absorption  of  cerebro-spinal 
fluid  into  the  veins.  On  our  present  knowledge  we  are  therefore 
justified  in  assuming  that  the  cerebro-spinal  fluid  is  secreted  by  the 
choroid  plexuses,  and  absorbed  by  the  cerebral  veins  and  the  longitudinal 
sinus.  An  increase  in  the  amount  of  the  cerebro-spinal  fluid  in  the  sub- 
arachnoid space  must  be  due  either  to  increased  rapidity  of  secretion, 
or  decreased  rapidity  of  absorption,  or  possibly  to  both  these  factors. 
We  have  no  direct  evidence,  at  present,  as  to  which  of  these  two 
factors  plays  the  chief  part  in  the  increase  of  pressure  found  in  cerebro- 
spinal fever.     The  choroid  plexuses  are  undoubtedly  involved  in  the 


viii]  Pathology  97 

■inflammatory  changes,  that  forming  the  roof  of  the  4th  ventricle  being 
always  affected;  it  is  probable  that  hyper-secretion  therefore  takes 
place.  On  the  other  hand  the  purulent  exudate  around  the  cerebral 
veins,  as  they  run  in  the  sub-arachnoid  space,  and  the  inflammatory 
reaction  of  the  venous  walls  themselves  may  considerably  hamper  the 
normal  absorptive  mechanism :  the  pacchionian  bodies  are  also  involved 
in  the  inflammatory  reaction.  It  is  thus  reasonable  to  suppose  that 
both  factors  plaj''  a  part  in  the  increase  in  the  amount  and  tension  of 
the  cerebro-spinal  fluid  in  cerebro-spinal  fever. 

The  distribution  and  nature  of  the  lesions  found  post-mortem 
vary  considerably,  according  to  the  duration  of  the  illness.  The 
pathological  conditions  found  will  therefore  be  described  separately, 
according  to  the  chnical  groupings  already  given.  The  following  types 
will  be  distinguished  :  the  fulminating  type,  in  which  a  fatal  termination 
occurs  within  48  hours ;  the  acute  type,  in  which  the  average  duration 
of  illness  is  under  five  days ;  the  sub-acute  type,  lasting  from  two  to 
four  weeks ;  and  the  chronic  hydrocephalic  type,  lasting  six  weeks  or 
more.  This  last  group  includes  the  majority  of  the  sporadic  cases  in 
infants,  which  may  last  even  as  long  as  nine  months. 

In  the  fulminating  type  the  duration  of  the  disease  is  less  than 
48  hours.  Even  though  the  disease  has  only  lasted  for  so  short  a  time, 
the  involvement  of  the  meninges  is  already  marked,  and  forms  the 
most  noticeable  feature  of  the  pathological  condition.  We  have  already 
referred  to  certain  cases  coming  under  our  own  observation  which 
demonstrated  this  very  clearly.  We  hold  that  even  in  these  fulminating 
cases  the  infection  chiefly  involves  the  brain  and  cord  only,  and  that 
a  septicaemic  stage  of  the  disease  cannot  be  considered  to  be  proved. 
The  meningococcus  does  however  on  rare  occasions  directly  invade  the 
blood  stream  so  as  to  cause  a  true  acute  septicaemia  which  is  rapidly 
fatal.  This  is  definitely  proved  by  the  case  of  Andrewes  already  quoted. 
The  absence  of  meningitis  in  this  form  is  very  striking,  and  has  already 
been  described.  Post-mortem  little  is  to  be  found  beyond  haemorrhages 
in  the  skin,  giving  rise  to  a  purpuric  rash,  and  also  similar  haemorrhages 
on  internal  surfaces.  The  existence  of  this  true  septicaemic  form  of 
infection,  in  which  the  cerebro-spinal  system  completely  escapes,  to- 
gether with  the  marked  cerebral  lesions  in  the  fulminating  type,  form 
a  strong  argument  against  the  view  that  the  infection  is  usually 
primarily  an  infection  of  the  blood,  which  settles  later  on  the  meninges. 

The  morbid  anatomy  of  the  true  fulminating  type  is  as  follows.  On 
examining  the  brain  the  dura  mater  is  often  more  adherent  than  usual 


98  Pathology  [cH. 

to  the  underlying  cortex  and  its  membranes.  On  exposing  the  surface' 
of  the  brain,  a  most  intense  congestion  of  the  cerebral  vessels  is  seen 
over  the  whole  vertex.  The  perivascular  sub-arachnoid  spaces  already 
contain  scattered  patches  of  pus  in  a  cloudy  serous  exudate;  the 
convolutions  are  slightly  flattened.  The  base  of  the  brain  is  in  a  similar 
condition;  the  sub-arachnoid  spaces,  such  as  the  cisterna  basaUs,  are 
distended  with  a  cloudy  serous  exudate,  with  occasional  patches  of  pus. 
This  exudate  is  seen  extending  down  the  cord.  On  opening  the  brain 
practically  no  distension  of  the  ventricles  is  to  be  found.  On  opening 
the  spinal  canal  and  dividing  the  theca,  an  excess  of  fluid  escapes. 
The  whole  surface  of  the  cord  is  extremely  congested,  with  here  and  there 
commencing  patches  of  pus  lying  over  the  vessels.  Microscopically 
the  changes  are  seen  to  be  almost  entirely  confined  to  the  meninges, 
both  in  the  brain  and  cord,  and  to  consist  of  an  intense  polymorpho- 
nuclear infiltration,  which  is  most  marked  roimd  the  congested  vessels, 
and  does  not  at  this  early  stage  extend  any  distance  into  the  sulci. 

The  changes  in  other  organs  are  those  due  to  the  intense  infection. 
Purpuric  spots  are  widely  distributed  over  the  skin,  being  especially 
marked  wherever  pressure  occurs,  such  as  the  knees  and  hips.  Similar 
haemorrhagic  spots  are  also  found  over  internal  surfaces,  such  as  the 
pleura,  pericardium  and  peritoneum.  The  right  side  of  the  heart  is 
distended;  the  muscle  is  macroscopically  normal.  The  liver  and 
kidneys  shew  cloudy  swelhng;  the  spleen  is  not  enlarged  or  soft. 
The  lungs  may  shew  some  purulent  exudate  in  the  bronchi;  this  is 
probably  a  secondary  effect  due  to  the  cerebral  condition.  In  one 
case  we  have  found  a  marked  haemorrhagic  infiltration  of  the  cortex 
and  medulla  of  the  suprarenals. 

In  the  acute  fatal  type  the  duration  of  illness  is  about  five  days. 
The  brain  and  cord  are  the  chief  organs  affected,  in  some  cases  practically 
no  change  can  be  found  in  the  other  organs  of  the  body.  In  the 
brain  (Plate  VII),  there  is  an  extremely  severe  congestion  over  the 
whole  of  the  vertex,  the  intense  engorgement  of  vessels  causing  the 
organ  to  appear  deep  red.  The  purulent  exudate  in  the  sub-arachnoid 
space  round  the  vessels  is  often  very  considerable,  and  widely  dis- 
tributed over  the  whole  organ;  the  most  intense  purulent  infiltration 
is  frequently  over  the  uppermost  part  of  the  vertex.  The  base  of  the 
brain  is  in  a  similar  condition,  but  very  frequently  the  purulent  exudate 
is  here  not  so  extensive  as  over  the  vertex.  The  olfactory  lobes  in 
some  cases  are  also  covered  with  pus,  and  abnormally  adherent  to  the 
cribriform  plate.     There  is  a  considerable  excess  of  cloudy  fluid  in  the 


viii]  Pathologij  09 

sub-arachnoid  spaces.  On  opening  the  brain,  the  ventricles  frequently 
contain  an  excess  of  fluid.  The  amount  of  fluid,  both  here  and  in  the 
sub-arachnoid  space,  depends  to  some  extent  upon  whether  lumbar 
puncture  has  been  recently  performed.  On  opening  the  theca  to  expose 
the  cord  (Plate  X,  fig.  1),  an  excess  of  purulent  fluid  escapes.  The 
vessels  are  extremely  congested.  The  amount  of  pus  present  varies 
considerably,  in  some  cases  very  little  is  found,  in  others  a  con- 
siderable amoimt  is  present.  This  is  more  frequently  situated  in  the 
lower  dorsal  and  lumbar  region  than  in  the  cervical.  In  this  type 
the  amount  of  pus  found  varies  considerably  both  over  the  brain  and 
over  the  cord;  it  is,  however,  never  completely  absent  in  either 
region,  and  is  usually  most  marked  over  the  vertex  of  the  brain. 
Microscopically  the  infection  is  again  found  to  be  in  the  main  con- 
fined to  the  meninges.  Purulent  exudate  is  now  extensive,  though 
still  most  intense  ro\md  the  vessels.  In  many  regions  the  whole  sub- 
arachnoid space  is  filled  with  cells,  pol_ymorphonuclear  leucocytes, 
which  here  and  there  are  beginning  to  shew  fatty  degeneration,  greatly 
predominating.  A  few  lymphocytes  and  larger  cells  with  round  nuclei 
are  also  present.  It  has  been  stated  that  eosinophil  cells  are  completely 
absent ;  this,  however,  is  certainly  not  the  case,  as  we  have  found  them 
to  be  present  fairly  frequently  in  scanty  numbers.  The  polymorpho- 
nuclear exudate  dips  right  down  into  the  sulci  with  the  pia  mater,  and 
also  extends  to  a  greater  or  less  extent,  with  the  larger  vessels,  from  the 
pia  into  the  brain  substance  as  a  perivascular  infiltration.  The  outer 
surface  of  the  cortex  itself  becomes  slightly  involved,  a  few  scattered 
polymorphonuclear  leucocytes  being  found  in  its  outermost  zone. 
According  to  Netter  a  greater  or  less  amount  of  oedema  occurs  in  this 
outermost  zone,  and  may  be  conspicuous  in  certain  localized  patches. 
He  also  describes  slight  changes  in  the  nerve  cells  themselves,  such  as 
chromatolysis  and  vacuolisation.  In  our  experience  these  changes,  if 
present,  are  extremely  shght ;  the  complete  and  rapid  recovery,  which 
may  take  place  in  a  case  appearing  at  the  onset  as  severe  as  the 
acute  fatal  cases,  negatives  the  common  occurrence  of  any  marked 
pathological  change  in  the  substance  of  the  brain  itself.  The  conditions 
in  the  cord  are  similar  to  those  in  the  brain :  according  to  Netter  some 
slight  degeneration  may  occur  in  the  sheaths  of  the  outermost  tract 
fibres,  this  is  however  most  common  at  a  somewhat  later  stage  in  the 
sub-acute  group.  The  amount  of  degeneration  is  in  any  case  extremely 
slight.  The  perivascular  polymorphonuclear  infiltration  may  be  of  con- 
siderable intensity  in  the  cord,  especially  affecting  the  posterior  horns. 

7—2 


100  Pathology  \(m. 

lu  one  of  our  cases  the  infection  was  so  acute  tliat  perivascular  haemor- 
rhages of  considerable  extent  had  occurred  both  in  the  substance  of  the 
cord  and  of  the  cortex  of  the  brain;  these  were  conspicuous  macro- 
scopically  as  small  red-brown  flecks.  They  were  most  intense  in  and 
around  the  posterior  horns  of  the  cord,  but  were  also  to  be  found  in 
the  substance  of  the  anterior  horns.  The  actual  site  in  which  meningo- 
cocci can  be  found  is  shewn  in  Plate  XI,  fig.  1 ;  they  lie  in  the  walls  of 
the  perivascular  spaces  which  surround  the  vessels  as  they  run  through 
the  sub-arachnoid  cavity,  and  can  be  found  at  times  in  considerable 
quantity  in  their  endothelial  lining.  They  are  difficult  to  find  in  the 
polymorphonuclear  leucocytes  in  sections  of  the  meninges ;  it  is  probable 
that  the}^  only  get  into  the  bodies  of  the  leucocytes  to  any  considerable 
extent  after  having  become  free  in  the  sub-arachnoid  cavity.  Ad- 
ditional evidence  in  support  of  this  view  is  afforded  by  the  examination 
of  successive  samples  of  the  fluid  withdrawn  at  a  particular  lumbar 
puncture.  Extracellular  forms  are  more  common  in  the  sample  of  the 
last  fluid  to  drain  away.  This  fluid  is  presumably  withdrawn  from  the 
immediate  neighbourhood  of  the  meninges  of  the  brain,  and  therefore 
contains  cocci  which  have  freshly  escaped  from  the  walls  of  the  peri- 
vascular spaces,  and  have  not  yet  become  ingested  by  the  leucocytes. 

The  pathological  changes  in  other  organs  are  comparatively  slight. 
The  occurrence  of  a  petechial  rash  is  variable.  In  no  case  are  the 
spots  as  large  as  in  the  purpuric  rash  of  the  fulminating  form.  Herpes 
is  also  occasionally  present  round  the  mouth.  The  liver  and  kidneys 
shew  a  greater  or  less  amount  of  cloudy  swelling;  but  this  is  re- 
markably slight  when  the  intense  nature  of  the  disease  is  taken  into 
consideration.  No  marked  changes  are  found  in  any  other  organs ; 
the  lungs  may,  however,  shew  the  beginning  of  a  secondary  bronchial 
infection. 

The  sub-acute  type  has  a  duration  of  two  to  four  weeks.  Untreated 
cases  may  succumb  at  this  stage.  The  condition  is  similar  to  that 
already  described,  but  the  distribution  of  pus  over  the  vertex  of  the 
brain  is  not  so  widespread,  and  the  congestion  is  not  so  intense;  the 
pus  is  more  markedly  distributed  at  the  base  of  the  brain  and  down 
the  cord.  There  is  a  marked  increase  of  cerebro-spinal  fluid  in  the 
sub-arachnoid  space,  both  around  the  base  of  the  brain  and  down  the 
cord. 

Another  form  also  occurs,  which  we  have  called  the  suppurative 
type.  Here,  though  lumbar  puncture  is  repeatedly  performed,  the  pus 
so  removed  becomes  thicker  and  thicker,  until  finally  only  a  small 


vm]  Pathology  101 

quantity  of  thin  serum  can  be  drained  off.  In  such  a  case  (Plate  VIII) 
the  base  of  the  brain  is  found  to  be  thickly  coated  with  a  dense  adherent 
purulent  mass,  which  completely  obscures  the  underlying  structures,  and 
through  which  the  nerves  can  be  seen  emerging.  Pus  is  also  foxmd 
scattered  scantily  over  the  vertex,  but  the  amount  is  insignificant 
compared  to  the  large  collection  at  the  base;  the  cerebral  vessels  are 
not  markedly  congested.  The  cord  (Plate  X,  fig.  2)  is  also  thickly 
covered  throughout  its  length  by  a  similar  dense  purulent  exudate, 
which  may  completely  fill  the  intrathecal  space,  and  thus  clothe  the 
cord  throughout  its  whole  length.  If  these  cases  have  been  lumbar 
punctured,  little  increase  of  actual  fluid  is  found  post-mortem.  This 
absence  of  fluid  is  in  most  striking  contrast  with  the  increase  found  in 
all  other  fatal  forms  of  the  disease  that  have  lasted  over  48  hours. 
The  marked  alteration  in  the  character  of  the  fluid  obtained  by  lumbar 
puncture  has  already  been  described  in  Chapter  V.  It  appears  that  for 
some  unknown  reason  the  purulent  exudate  gets  more  and  more  inspis- 
sated, and  is  at  the  same  time  accompanied  by  less  and  less  free  fluid 
in  the  sub-arachnoid  spaces.  The  reason  for  this  extremely  fatal  course 
in  certain  cases  is  at  present  imknown.  The  character  of  the  consecutive 
punctire  fluids  sufiiciently  indicates  that  the  case  is  of  this  type. 

In  this  sub-acute  group  the  condition  has  lasted  sufficiently  long 
for  considerable  general  wasting  to  occur.  Changes  in  other  organs  are 
inconspicuous.  Broncho-pneumonic  changes  in  the  lung  are,  however, 
frequent,  the  infection  commonly  being  pneumococcal.  This  can  be 
looked  upon  as  a  secondary  complication,  owing  to  the  terminal 
comatose  state  of  these  patients. 

In  the  chronic  type,  with  a  history  of  six  weeks  or  more,  a  marked 
difference  is  present  owing  to  the  development  of  hydrocephalus.  The 
brain  (Plate  IX,  fig.  1)  shews  considerable  flattening  of  the  convolutions. 
The  meninges  over  the  vertex  shew  little  sign  of  pus,  and  no  congestion 
of  the  vessels.  A  certain  amount  of  pus  may  still  be  present  at  the  base 
of  the  brain,  but  in  many  cases  it  is  entirely  absent.  Marked  thickening 
of  the  meninges  can  often  be  observed  in  this  situation.  On  opening 
the  ventricles,  a  large  amount  of  fluid,  usually  clear,  is  liberated; 
dilatation  is  most  marked  in  the  third  and  fourth  ventricles,  the  iter 
also  is  often  widely  dilated,  and  the  lateral  ventricles  may,  or  may  not, 
take  part  in  the  condition.  If  dilatation  of  the  lateral  ventricles  is 
present,  the  foramina  of  Munro  are  very  conspicuous.  The  cord,  in 
correspondence  with  the  base  of  the  brain,  may  or  may  not  be  covered 
here  and  there  with  a  certain  amount  of  pus.     The  complete  or  almost 


102  Pathology  [oh. 

complete  absence  of  pus  over  the  brain  and  cord,  which  is  usual  in 
hydrocephalic  cases  of  long  standing,  may  give  rise  to  doubt  whether 
a  particular  case  has  really  died  as  the  result  of  cerebro-spinal  fever, 
if  proof  has  not  been  obtained  by  lumbar  puncture  in  the  acute  stage. 
The  theca  is  often  adherent  to  a  greater  or  less  extent  to  the  cord. 
This  adherence  may  be  so  extensive  as  to  occlude  completely  the 
sub-thecal  space,  as  is  shewn  in  Plate  X,  fig.  3.  In  consequence  of 
the  formation  of  such  an  adhesion,  lumbar  puncture  ceases  to  reheve 
the  pressure  in  the  upper  part  of  the  cord  and  the  brain.  This  was 
the  case  in  the  patient  whose  cord  is  here  shewn.  A  very  great 
distension  by  fluid  under  pressure  was  present  above  the  point  of 
complete  adhesion,  while  the  theca  below  this  was  empty.  In  other 
cases,  although  the  ventricles  are  distended  with  fluid,  do  excess  is 
found  in  any  region  of  the  cord.  The  adherence  of  the  roof  of  the 
fourth  ventricle  to  the  cerebellum  overlying  it  has  occluded  the  paths 
of  communication  between  the  cavity  of  the  ventricle  and  the  cisterna 
magna.  Here  also  lumbar  puncture  has  failed  to  relieve  the  intra- 
ventricular pressure,  and  a  large  amount  of  fluid  is  found  in  the 
distended  ventricles.  In  these  chronic  cases  wasting  is  very  marked 
and  in  long-standing  cases  may  be  of  extreme  degree.  Other  organs 
shew  no  characteristic  changes.  Cystitis  of  the  bladder  is  present  in 
some  cases,  the  infection  of  this  organ  being  secondary  to  prolonged 
retention  and  incontinence. 

From  this  description  of  post-mortem  appearances  at  various  stages 
of  the  disease,  it  is  clear  that  in  fatal  cases  infection  of  the  meninges 
is  not  confined  to  the  base  of  the  brain  in  the  early  stages;  on  the 
contrary,  in  the  acute  type  of  case,  the  meninges  over  the  vertex  of  the 
brain  are  the  most  conspicuously  affected.  It  is  only  in  the  more 
chronic  types  that  the  infection  tends  to  be  confined  mainly  to  the 
base.  Cases  which  recover,  and  even  recover  quickly,  when  first  seen 
may  appear  to  be  even  more  desperate  than  those  which  have  been 
described  as  the  acute  fatal  type ;  it  is  therefore  justifiable  to  look  upon 
infection  as  primarily  affecting  all  the  membranes  of  the  brain  and 
cord  in  every  case.  Its  locahzation  to  the  base  of  the  brain  would 
then  be  a  subsequent  development  in  the  more  chronic  and  milder  type 
of  case.  This  localization  is  never  complete,  it  can  only  be  said  that 
in  these  more  chronic  cases  the  bulk  of  the  exudate  is  situated  there. 

The  substantiation  of  a  diagnosis  of  cerebro-spinal  fever  in  the 
post-mortem  room  in  a  case,  which  has  not  been  punctured  in  life,  can 
only  be  indirectly  accomplished,  for  a  culture  of  the  meningococcus 


vni]  Pathology  103 

is  almost  impossible  to  obtain  after  death.  Smears  from  the  purulent 
exudate  will  however  often  demonstrate  the  presence  of  intracellular 
gram-negative  diplococci.  A  negative  culture  is  also  of  considerable 
importance,  for  practically  all  the  other  organisms,  which  bring  about 
a  purulent  meningitis,  can  easily  be  cultured  from  the  brain  at  the 
post-mortem. 

In  hydrocephaHc  cases,  with  httle  or  no  pus,  organisms  are  seldom 
found  in  films.  The  development  of  hydrocephalus  is  an  extremely 
serious  sequel ;  it  can  in  many  cases  be  combated  and  perhaps  prevented 
by  frequent  lumbar  puncture,  beginning  as  early  as  possible  in  the  disease. 
The  occurrence  of  scarring,  so  as  to  occlude  the  circulation  of  the  cerebro- 
spinal fluid,  either  between  the  central  ventricles  and  the  sub-arachnoid 
space,  or  in  the  sub-arachnoid  space  itself,  necessarily  prevents  relief 
being  obtained  by  lumbar  puncture.  The  reason  for  the  increase  in 
pressure  of  the  cerebro-spinal  fluid  cannot  at  present  be  completely 
explained,  as  we  are  ignorant  of  many  points  in  the  normal  circulation 
of  this  fluid.  It  has  been  already  stated  that  the  balance  of  evidence 
is  at  present  in  favour  of  the  view  that  the  fluid  is  secreted  by  the 
choroid  plexuses,  and  that  it  drains  ofE  by  channels  into  the  venous 
sinuses  of  the  skull.  The  increased  pressure  in  the  earher  stages  is 
doubtless  inflammatory  in  origin,  and  this  inflammation,  in  addition  to 
considerable  increase  of  secretion,  may  also  cause  temporary  occlusion 
of  the  channels  of  drainage.  The  conditions  are  strictly  similar  to 
those  found  in  a  circumscribed  inflammation  of  other  tissues,  in  which 
the  inflammatory  swelHng  demonstrates  the  temporary  inadequacy  of 
drainage.  The  increase  of  pressure  in  the  chronic  type  with  hydro- 
cephalus would  appear  to  be  due  in  part  to  scarring  and  consequent 
obliteration  of  the  normal  channels  of  drainage. 

The  identity  of  posterior  basic  meningitis  of  infants  with  the  chronic 
form  of  epidemic  meningitis  is  almost  certain.  Still,  however,  who 
identified  a  gram-negative  diplococcus  as  the  cause  of  the  former  disease, 
questioned  the  identity  of  his  organism  with  the  meningococcus  of 
Weichselbaum.  He  based  his  conclusions  mainly  on  the  evidence  of 
agglutination  reactions.  When,  however,  we  consider  that  the  agglu- 
tinative properties  of  various  gram-negative  diplococci,  which  have  been 
obtained  from  the  cerebro-spinal  fluid  of  cases  of  epidemic  meningitis, 
also  vary  very  greatly  in  this  respect,  this  criticism  loses  its  value. 
Still's  organism  can  be  grouped  with  these  other  variable  organisms 
which  come  under  the  designation  of  the  meningococcus.  The  disease 
as  it  affects  adults  is  remarkably  free  from  comphcations,  other  than 


104  Pathology  [ch. 

those  already  given;  the  occurrence  of  paralysis  is  uncommon,  and 
when  such  lesions  do  occur  they  are  usually  transient.  In  children, 
however,  especially  in  the  chronic  forms,  paralyses  occur  and  are 
sometimes  permanent.  A  good  many  of  the  permanent  paralyses 
recorded  in  the  earlier  hterature  were  probably  to  be  accounted  for 
by  errors  in  diagnosis,  acute  anterior  poliomyehtis  being  confused 
with  epidemic  meningitis.  The  more  modem  hterature  tends  to 
the  view  that,  even  in  children,  permanent  paralyses  are  very 
rare.  Liebermeister  has  described  the  pathological  conditions  in 
cases  of  permanent  paralysis;  they  consist  of  degeneration  of 
anterior  horn  cells  and  a  degeneration  of  the  posterior  nerve  roots, 
resulting  from  the  purulent  infiltration  surrounding  them.  One  com- 
plication, however,  is  not  uncommon,  especially  in  the  posterior  basic 
type,  namely  permanent  blindness,  which  is  probably  central  in  origin. 
Direct  extension  of  the  meningococcal  infection  from  the  nose  to 
the  eye  occasionally  gives  rise  to  iridocyclitis  or  panophthalmitis. 
Another  comphcation,  especially  in  children,  is  the  occurrence  of 
arthritis.  This,  however,  hardly  ever  gives  rise  to  changes  in  the 
joint  which  can  be  identified  post-mortem.  kSuppuration  is  very  rare. 
The  meningococcus  has  occasionally  been  recovered  from  such  joints. 

The  occurrence  of  the  meningococcus  in  the  blood  will  be  discussed 
in  the  next  chapter.  Certain  cases  have  been  recorded  by  Andrewes 
and  others,  in  which  the  meningococcus  has  been  the  cause  of  a  fulminat- 
ing septicaemia  mthout  clinical  or  pathological  evidence  of  meningitis. 
The  recorded  number  of  such  cases  is,  however,  extremely  few.  Even 
in  the  fulminating  type,  described  above,  lasting  24  hours  or  less, 
marked  evidence  of  meningitis  is  to  be  found.  A  meningococcal 
endocarditis  has  been  recorded,  but  is  to  be  accepted  with  reserve  owing 
to  the  difficulty  of  diagnosing  the  meningococcus  from  the  gonococcus. 

Two  views  have  been  advanced  as  to  the  method  by  which  the 
meningococcus  penetrates  to  the  central  nervous  system.  All  present 
evidence  leads  to  the  view  that  the  common  harbourage  of  the  meningo- 
coccus in  the  body  is  the  posterior  pharj^nx  and  upper  regions  of  the 
nose.  This  is  the  region  from  which  the  organism  can  be  obtained  in 
carriers,  being  often  present  in  almost  pure  culture.  It  has  therefore 
been  advanced  that  the  path  of  entry  may  be  a  direct  one  from  the 
nose,  or  its  accessory  sinuses,  to  the  brain  itself.  The  most  probable 
path  is  along  the  olfactory  nerves  to  the  olfactory  lobes,  and  thence 
to  the  base  of  the  brain.  A  variant  path  has  been  lately  suggested 
by  Embleton,  namely,  that  the  sphenoidal  sinuses  become  early  infected. 


vin]  Pathology  105 

and  that  the  organism  penetrates  from  them  by  lymphatic  channels 
directly  to  the  base  of  the  brain .  This  view  is  similar  to  that  advanced 
by  Westenhofl'er,  who  maintained  that  the  parts  of  the  brain  round  the 
hypophysial  gland  were  first  infected.  The  second  view  is  that  the 
infection  is  primarily  a  septicaemia,  but.  that  the  organism  has  a 
selective  affinity  for  the  central  nervous  system,  and  thus  settles  there. 
The  evidence  for  this  second  view  consists  in  the  obtaining  of  positive 
blood  cultures.  Seeing  that  such  cultures  can  only  be  obtained  by 
using  large  quantities  of  blood,  and  then  only  in  a  comparatively  small 
percentage  of  cases,  it  may  be  argued  that  the  infection  of  the  blood 
is  derived  from  the  meninges,  rather  than  that  the  infection  of  the 
meninges  is  derived  from  the  blood.  Elser  and  Huntoon  only  obtained 
a  positive  blood  culture  in  eleven  out  of  forty-one  cases,  and  in  three  of 
these  a  subsequent  re-examination  of  the  blood  a  short  time  afterwards 
proved  negative;  one  re-examination  only  was  positive.  Pus,  in  which 
meningococci  can  be  found  in  smears,  is  easily  demonstrable  in  certain 
cases  on  the  olfactory  lobes,  which  are  often  unduly  adherent  to  the 
cribriform  plate ;  facts  which  lend  support  to  the  view  of  invasion  by 
the  direct  path  along  the  olfactory  nerves.  The  relationship  of  the 
dura  mater  to  the  wall  of  the  nose,  and  the  comparatively  free  con- 
nection of  the  sub-arachnoid  space  with  the  mucous  membrane  of  the 
nasal  cavity,  have  already  been  described.  This  anatomical  peculiarity 
of  the  olfactory  nerves  affords  an  exceptionally  easy  path  of  invasion 
to  an  organism  whose  characteristic  habitat  is  the  upper  part  of  the 
naso-pharynx.  The  matter  is  at  present  unsettled,  its  final  solution  is 
a  problem  which  involves  not  only  this  disease,  but  other  diseases,  for 
example,  lobar  pneumonia,  which  are  said  to  follow  upon  an  initial 
primary  septicaemia. 

The  general  reaction  of  the  body  to  the  invasion  by  the  meningo- 
coccus will  now  be  briefly  considered.  A  polymorphonuclear  leuco- 
cytosis  is  always  present  to  a  greater  or  less  extent.  The  count  usually 
averages  about  25,000  per  c.mm.  and  rarely  rises  as  high  as  50,000. 
The  exact  value  of  the  leucocyte  count  is  apparently  of  little  importance 
as  regards  prognosis.  A  low  count  may  be  obtained  either  in  a  mild 
case  or  in  a  severe  one.  The  presence  of  an  increased  leucocyte  count 
is  of  some  assistance  in  the  diagnosis  of  doubtful  cases,  as  in  some 
diseases  which  have  to  be  differentiated,  such  as  tuberculous  meningitis 
or  typhoid  fever,  no  increase  of  leucocytes  is  present  in  the  blood. 

The  alterations  in  the  serum  of  patients  suffering  from  the  disease 
have  mostly  been  studied  by  means  of  the  agglutination  reaction. 


106  Patliology  [CH. 

Von  Lingelsheim  and  others  have  studied  the  variations  in  agglutination 
reactions  of  the  sera  in  cases  of  cerebro-spinal  fever,  and  have  found 
that  there  is  a  great  variation  in  this  respect.  There  is  no  definite 
relationship  between  the  stage  of  the  disease  and  the  appearance  of  an 
agglutinating  reaction.  In  some  cases  serum  is  powerfully  agglutinating 
in  the  earliest  days,  in  others  an  increase  of  agglutinating  power  did 
not  appear  until  two  or  three  weeks  after  the  onset.  The  persistence 
of  an  agglutinating  capacity  also  varies  considerably,  but  usually  with 
recovery  it  is  rapidly  lost.  It  is  not  yet  certain  whether  the  aggluti- 
nating capacity  bears  much  relationship  to  the  severity  of  the  disease,  or 
whether  a  high  agglutinating  power  means  a  favourable  prognosis.  In 
the  chapter  on  the  properties  of  the  meningococcus  and  other  gram- 
negative  diplococci,  further  reference  will  be  made  to  the  difficulties  in 
the  investigation  of  the  agglutinative  power  of  any  particular  serum. 
The  agglutinative  value  of  a  particular  serum,  with  regard  to  different 
strains  of  meningococci,  varies  very  greatly  even  with  strains  which  have 
all  been  obtained  by  lumbar  puncture.  Studies  of  the  agglutinative 
power  of  the  serum  in  any  particular  patient  are  therefore  of  little 
value,  unless  carried  out  with  the  patient's  own  strain  of  organism. 
An  agglutination,  which  is  often  complete,  can  be  obtained  with  normal 
serum  at  a  dilution  of  1  in  10  with  many  strains,  if  the  macroscopical 
method  be  used  and  the  reactions  be  allowed  to  continue  for  four  days. 
The  agglutinative  power  of  a  serum  can,  therefore,  only  be  considered 
to  be  increased  when  complete  agglutination  takes  place  at  higher 
dilutions  than  this.  We  have  studied  the  agglutinative  power  of  the 
serum  of  a  few  chronic  cases  against  their  own  strains,  and  find  that, 
while  complete  agglutinations  may  take  place  with  a  dilution  as  high 
as  1  in  1000,  in  other  cases  the  agglutinative  power  may  be  even  below 
that  of  normal  serum. 

The  opsonic  value  of  the  serum  has  been  studied  by  McGregor  and 
others,  and  this  again  is  apparently  of  "httle  or  no  prognostic  value. 
Houston  and  Rankin  consider  that  a  high  opsonic  index  is  present  in 
most  cases  about  the  sixth  day  of  disease,  and  that,  at  this  period  and 
after,  the  opsonic  index  is  of  considerable  diagnostic  value.  Sophian, 
however,  finds  that  the  difficulties  in  the  opsonic  technique,  which  are 
present  in  all  such  estimations,  are  greatly  increased  in  the  case  of  the 
meningococcus  group,  so  that  estimations  are  very  unreliable;  those 
performed  with  any  strain  except  that  of  the  patient  in  question  giving 
widely  divergent  results.  The  opsonic  index  is  therefore  of  y&xj  little 
value  in  estimating  the  reaction  of  the  body  to  infection. 


vm]  Pathology  107 

Complement  fixation  has  also  been  studied  by  Meakins,  Dopter,  and 
Sophian  and  Neal,  and  they  have  shewn  the  presence  of  immune  bodies 
in  the  blood  by  this  method.  Sophian  and  Neal  have,  however,  found 
that  cross  fixation  occurs  between  the  meningococcus  and  the  gono- 
coccLis ;  the  reaction  as  at  present  studied  is  thus  not  sufficiently  specific 
to  be  of  diagnostic  value. 

Dopter  found  that  the  serum  of  patients  sufTering  from  the  disease 
was  actively  bactericidal  to  the  meningococcus.  Mackenzie  and  Martin 
introduced  the  serum  from  the  patient's  own  blood,  and  from  the  blood 
of  recovered  cases,  into  the  spinal  canal,  and  claim  favourable  results 
from  this  treatment.  We  also  have  introduced  his  own  serum  into  the 
spinal  canal  of  a  patient  suffering  from  a  fairly  mild  form  of  the  disease 
in  the  chronic  stage,  with  the  result  that  no  further  treatment  was 
necessary  and  convalescence  ensued.  It  appears,  therefore,  that 
immune  bodies  are  formed  in  the  blood  which  are  actively  bactericidal. 

To  sum  up:  our  present  evidence  of  the  constancy  of  production 
of  specific  protective  substances  in  the  blood  is  vague,  and  the  usual 
methods  of  estimating  these  are  difficult  of  application  in  the  case  of 
the  meningococcus.  Our  knowledge  of  the  time  of  appearance  of  these 
substances  and  their  persistence  is  also  scanty :  their  estimation  by  our 
present  methods  is  therefore  of  little  value  in  regard  to  prognosis. 
Evidence  is  however  accumulating  that  the  meningococcus  is  not  a 
single  organism  of  constant  properties,  but  should  rather  be  looked 
upon  as  a  group  of  related  organisms,  which  can  possibly  be  separated 
into  species  whose  properties  are  constant.  If  such  a  grouping  can  be 
substantiated,  serum  reactions  should  become  of  great  value  in  the 
prognosis  of  the  disease. 


CHAPTER  IX 

CHANGES  IN  THE  CEREBRO -SPINAL  FLUID  AND  THE  CULTI- 
VATION OF  THE  MENINGOCOCCUS  FROM  IT,  FROM  THE 
BLOOD   AND  FROM   THE   URINE 

The  normal  cerebrospinal  fluid,  its  changes,  increase  of  pressure. 
Alterations  in  the  chemical  constituents,  appearance,  albumen,  sugar. 
Alterations  in  the  cellular  constituents,  the  identification  of  the 
meningococcus  in  films,  theimportance  of  the  numbers  present.  Culture 
of  the  meningococcus  from  the  cerebrospinal  fluid,  from  the  blood, 
from  the  urine. 

The  study  of  the  cerebro-spinal  fluid  in  epidemic  meningitis  is  of 
the  greatest  importance ;  for  not  only  is  the  recovery  of  the  meningo- 
coccus from  it  essential  for  the  diagnosis  of  the  disease,  but  also  its 
frequent  removal  by  lumbar  puncture  is  one  of  the  most  important 
factors  in  treatment.  Its  study  is  also  of  considerable  value  with 
regard  to  prognosis,  as  an  improvement  in  the  characters  of  the  cerebro- 
spinal fluid  usually  coincides  with  an  improvement  in  the  course  of  the 
disease. 

The  normal  cerebro-spinal  fluid  is  a  perfectly  clear  colourless  Uquid 
of  a  low  specific  gravity,  being  usually  about  1-007 ;  its  reaction  is  faintly 
alkaline.  The  total  amount  present  is  generally  held  to  be  about  60  to 
80  c.c.  Estimations  of  its  normal  pressure  vary  considerably.  Accord- 
ing to  Peyton  Rous  it  may  vary  between  70  and  300  mm.  of  water. 
Quincke  gives  it  at  30  to  50  mm.  The  point  that  is  important  for 
practical  purposes  is  that  the  normal  pressure  is  such,  that,  when  lumbar 
puncture  is  performed,  the  fluid  flows  at  the  rate  of  about  one  drop 
every  2  or  3  seconds.  The  maximum  amount  which  can  be  obtained 
is  usually  less  than  10  c.c,  never  above  this.  The  fluid  pulsates  synchro- 
nously with  the  heart-beats.  Its  soUd  constituents  are  about  1  per  cent, 
of  the  total,  inorganic  salts  forming  the  major  portion  and  consisting 
chiefly  of  sodium  chloride.  There  are  also  present  small  amounts  of 
potassium  chloride,  phosphates  of  lime  and  magnesia,  and  traces  of  iron 


CH.  ix]  The  Cerebrospinal  Fluid  109 

and  sulphates.  Proteid  constituents  are  present  in  very  small  amounts, 
usually  forming  only  about  0-1  per  cent,  of  the  total.  These  proteids 
are  mainly  albumoses  and  globuhns  with  a  faint  trace  of  peptone. 
Albumen  is  normally  absent.  Boihng  the  cerebro-spinal  fluid  gives  an 
extremely  faint  cloud  or  none  at  all;  but  when  the  reaction  is  made 
acid  with  acetic  acid,  a  faint  cloud  usually  appears.  In  addition  to  the 
salts,  the  proteids,  and  a  trace  of  nitrogenous  extractives,  a  reducing 
substance  is  also  present.  The  reduction  obtained  with  FehUng's 
solution  is  appreciable,  being  easily  observed  on  allowing  the  fluid  to 
stand  and  cool.  It  was  originally  stated  by  Claude  Bernard  to  be 
sugar;  this  has  been  questioned  by  Halhburton,  who  holds  that  it  is 
pyrocatechin  and  is  a  decomposition  product  of  protein.  More  recent 
observers  have  however  reverted  to  the  view  that  it  is  glucose.  The 
cerebro-spinal  fluid  is  thus  similar  to  blood  plasma  with  practically  all 
its  proteid  constituents  left  out.  The  cellular  constituents  of  a  normal 
cerebro-spinal  fluid  are  extremely  scanty,  averaging  about  one  to  seven 
cells  per  c.mm.,  and  consist  of  lymphocytes  and  occasional  endothehal 
cells.     Polymorphonuclear  cells  are  absent. 

With  the  exception  of  the  presence  of  the  meningococcus,  the 
changes  in  the  cerebro-spinal  fluid  in  epidemic  meningitis  are  not 
pecuhar  to  this  disease,  but  occur  in  various  other  infections  of  the 
brain  and  cord  and  their  meninges.  These  changes  will  be  dealt  with 
under  the  various  headings  of  increase  of  pressure,  alteration  in  chemical 
constituents,  and  alteration  in  cellular  constituents. 

Increase  of  pressure  is  constantly  present  in  almost  all  stages  of  the 
disease.  The  increase  is  often  very  great,  so  that  on  performing  lumbar 
puncture  the  fluid  spurts  out  in  a  continuous  fountain.  Even  on  the 
first  day  of  the  disease  the  pressure  is  greatly  increased.  The  amount 
of  fluid  that  can  be  drawn  off  varies  very  considerably,  as  much  as 
40  c.c.  is  often  obtained  in  the  acute  stages.  In  the  chronic  stages,  in 
which  hydrocephalus  has  set  in,  even  larger  amounts  may  be  obtained, 
especially  if  the  patients  are  allowed  to  remain  a  number  of  days  without 
puncture.  In  some  chronic  cases  practically  no  fluid  can  be  with- 
drawn after  a  certain  stage :  this  is  of  serious  import,  as  it  means 
that  complete  occlusion  has  taken  place  in  the  sub-arachnoid  space. 
This  occlusion  has  already  been  described,  and  occurs  either  at  some 
level  in  the  cord  itself,  or  at  the  openings  of  the  fourth  ventricle  into  the 
cisterna  magna.  The  removal  of  cerebro-spinal  fluid  can  be  continued 
until  the  flow  is  equal  to  or  even  less  than  the  normal,  with  no  danger 
to  the  patient  when  he  is  under  a  general  anaesthetic.     Sophian  has 


110  The  Cerebrospinal  Fluid  [ch. 

studied  the  blood  pi  assure  before  and  after  lumbar  puncture,  and  finds 
that  a  shght  drop  of  pressure  most  commonly  occurs ;  in  some  cases  no 
change  is  to  be  found,  and  in  a  few  a  rise  of  pressure  takes  place. 
Though  the  complete  relief  of  increased  cerebro-spinal  pressure  is  thus 
without  danger,  the  re-establishment  of  raised  pressure,  which  the  intro- 
duction of  serum  involves,  may  produce  definite  ill  effects,  even  when 
the  final  pressure  is  considerably  below  that  before  puncture.  Sophian 
finds  that  the  injection  of  serum,  in  amounts  even  considerably  less  than 
that  of  the  cerebro-spinal  fluid  withdrawn,  may  cause  a  very  large  and 
alarming  fall  in  the  blood  pressure;  the  injection  of  serum  in  lesser 
amounts  also  causes  a  shght  fall  of  usually  from  11  to  15  mm.  of 
mercury.  He  therefore  considers  that  the  blood  pressure  should  be 
watched  while  injecting  serum,  and  that  considerably  less  serum  should 
be  introduced  than  the  amount  of  cerebro-spinal  fluid  withdrawn.  The 
rate  of  injection,  and  therefore  the  more  or  less  rapid  re-establishment  of 
increased  cerebro-spinal  pressure,  is  also  an  important  factor,  a  rapid 
introduction  of  serum  often  giving  rise  to  a  considerable  fall  in  blood 
pressure.  The  relief  of  symptoms  after  puncture  and  removal  of  the 
excessive  cerebro-spinal  pressure  is  almost  always  marked,  the  amount 
of  head  retraction-  decreasing,  consciousness  returning  and  headache 
diminishing.  In  chronic  cases  the  patient  often  obtains  so  much  relief 
from  this  procedure,  that  he  begs  for  puncture  to  be  done  at  frequent 
intervals.  Increase  of  pressure  is  therefore  partly  responsible  for  many 
of  the  symptoms  of  the  disease,  even  in  the  early  stages,  and  its  reUef 
is  markedly  beneficial.  In  the  chronic  stages  the  increase  of  pressure 
plays  an  even  more  important  part,  and  such  patients  usually  die  from 
respiratory  failure,  due  to  excessive  pressure  on  the  respiratory  centre 
in  the  fourth  ventricle.  The  introduction  of  serum  is  from  this  point 
of  view  of  questionable  benefit,  as  it  replaces  the  pressure  which  has  been 
relieved  by  the  lumbar  puncture.  The  chnical  rehef ,  which  is  so  marked 
after  simple  puncture,  is  usually  absent  when  serum  has  been  introduced, 
the  patient  being  often  temporarily  worse  than  before  puncture.  Unless 
therefore  the  serum  can  be  proved  definitely  to  remove  the  infective 
agent  more  quickly  than  simple  drainage  by  puncture,  the  latter  treat- 
ment is  on  all  grounds  a  preferable  one. 

An  increase  of  pressure  in  the  cerebro-spinal  fiuid  is  by  no  means 
pecuhar  to  meningitis.  Besides  being  present  in  other  cerebral  con- 
ditions, such  as  tumour,  the  pressure  is  frequently  found  to  be  consider- 
ably increased  in  certain  febrile  diseases,  for  instance,  pneumonia  and 
infiuenza.     As  much  as  30  c.c.  can  often  be  obtained  in  these  diseases. 


ix]  The  Cerebrospinal  Fluid  111 

Owing  to  the  difficulty  of  diagnosis  at  an  early  stage  of  illness,  a 
considerable  number  of  such  cases  rightly  undergo  a  diagnostic  lumbar 
prmcture.  The  mere  presence  of  a  marked  increase  of  pressure  is  of  no 
value  in  difierentiation. 

Alterations  in  the  chemical  constituents  are  considerable.  In  acute 
stages  of  the  disease  the  appearance  of  the  cerebro-spinal  fluid  is  pro- 
foundly altered.  When  first  withdrawn  it  is  opalescent  or  cloudy,  or 
may  contain  actual  fragments  of  purulent  material,  which  soon  sink  to 
the  bottom.  If  it  is  allowed  to  stand  for  some  httle  time,  the  cells 
suspended  in  it,  to  which  its  cloudiness  is  due,  sink  to  the  bottom  and  the 
supernatant  fluid  becomes  clear.  In  the  later  stages  of  the  disease  the 
fluid  may  become  clear  and  appear  hke  ordinary  cerebro-spinal  fluid. 
The  amount  of  pus  present,  as  judged  by  the  deposit  on  standing  or 
centrifugalizing,  is  of  considerable  importance  with  regard  to  the  course 
of  the  disease.  In  the  acute  stages  a  small  amount  of  pus  is  usually  of 
favourable  import,  whereas  a  large  amount  is  unfavourable.  Fulminating 
cases  may  yield  very  little  pus,  since  from  their  nature  lumbar  puncture 
is  necessarily  performed  soon  after  onset.  If  lumbar  puncture  be  per- 
formed at  an  equally  early  stage  in  other  cases,  the  fluid  will  hkewise 
be  found  to  contain  very  Httle  pus.  Another  matter  of  considerable 
importance  is  the  variation  of  the  amount  of  purulent  deposit  in  a  series 
of  puncture  fluids.  In  an  acute  case,  which  runs  a  favourable  course, 
the  deposit  may  increase  for  the  first  few  days,  it  then,  however,  pro- 
gressively diminishes.  In  cases  which  do  not  react  to  treatment,  pus 
tends  to  increase  progressively.  The  alterations  in  the  suppurative  type 
of  case,  which  terminates  fatally,  are  characteristic,  the  amount  of 
deposit  increases  at  each  puncture  and  the  fluid  becomes  thicker  and 
thicker,  until  at  last  the  pus  becomes  so  thick  that  it  will  not  flow 
through  the  puncture  needle,  and  only  a  small  amount  of  thin  serum  can 
be  obtained.  The  reason  for  this  latter  development  is  explained  post- 
mortem ;  the  cord  is  found  coated  with  pus  of  an  extremely  thick  and 
adherent  character.  In  the  chronic  forms,  with  development  of  hydro- 
cephalus, the  fluid  tends  to  clear  after  about  the  fifth  or  sixth  week; 
in  these  cases  it  is  remarkable  how  clear  a  fluid  may  yield  a  positive 
culture  of  the  meningococcus.  A  hydrocephalic  case  of  long  standing 
often  yields  a  fluid  so  clear  as  to  be  indistinguishable  from  the  normal. 
In  addition  to  the  variations  in  opacity  due  to  the  relative  amount 
of  pus,  another  change  may  occasionally  be  observed ;  the  fluid  becomes 
increasingly  yellow,  until  it  may  ultimately  be  a  deep  straw  colour. 
The  nature  of  the  pigment  which  causes  this  is  at  present  undetermined. 


112  The  Oerehro-spinal  Fluid  [ch. 

It  gives  no  bands  in  the  spectrum  and  is  therefore  not  a  derivative  of 
haemoglobin ;  it  can  be  extracted  by  chloroform  but  in  such  an  extract 
it  fades  fairly  quickly.  This  pigmentation  may  occur  either  in  the 
presence  of  a  large  amount  of  pus  or  in  a  practically  clear  fluid.  It 
usually  accompanies  the  presence  of  a  considerable  amount  of  albumen. 
It  must  not  be  confused  with  the  colour  which  may  be  imparted  to  the 
fluid  by  the  presence  of  a  small  amount  of  blood,  and  is  usually  due 
to  the  pricking  by  the  puncture  needle  of  the  extensive  venous  plexus 
lying  on  the  ventral  aspect  of  the  spinal  canal.  The  wounding  of  this 
plexus  may  yield  a  deeply  blood-stained  puncture  fluid  which  clots,  or 
may  only  cause  comparatively  faint  staining  of  the  fluid.  We  have  met 
with  this  change  in  colour  both  comparatively  early  in  acute  cases,  and 
late  in  hydrocephaUc  conditions.  It  appears  to  have  no  serious  signi- 
ficance, since  it  has  been  observed  both  in  cases  which  recovered  and 
in  fatal  cases.  When  the  amount  of  pus  present  is  small,  the  fluid 
on  standing  frequently  yields  a  fine  gelatinous  clot.  This  has  been 
claimed  as  characteristic  of  tubercular  meningitis,  but  is  also  quite 
common  at  various  stages  in  epidemic  meningitis. 

The  chief  alterations  of  constituents,  which  are  in  solution, 
consist  in  an  increase  of  the  protein  present  and  a  diminution  of  the 
sugar.  The  protein  is  chiefly  albumen,  and  may  be  present  in  such 
quantity  as  to  give  a  flocculent  precipitate  on  boihng.  It  is  always 
increased  even  in  the  late  hydrocephahc  stages,  the  amount  present 
in  an  apparently  clear  fluid  often  being  large.  The  sugar  is  practically 
always  diminished,  but  is  not  necessarily  absent  even  in  the  acute 
stages.  In  the  majority  of  these,  however,  the  amount  is  so  small  that 
it  fails  to  yield  a  precipitate  with  Fehhng's  test.  With  improvement 
in  the  chnical  condition  the  sugar  slowly  returns.  A  not  uncommon 
course  is  an  increasing  diminution  of  reduction  for  the  first  three  or 
four  days,  a  complete  absence  for  any  number  of  days  up  to  a  week, 
and  then  a  gradual  return  of  reducing  power.  In  the  chronic  stages 
an  appreciable  amount  of  sugar  is  usually  present,  but  is  seldom  equal 
to  the  normal.  In  the  suppurative  cases,  with  progressive  increase  in 
the  amount  of  pus,  the  sugar  is  as  a  rule  completely  absent  throughout. 
The  amount  of  albumen  present  is  of  httle  prognostic  value.  The 
persistent  absence  of  sugar  is  of  serious  import,  but  the  value  of  this 
test  is  not  great,  other  indications  being  of  more  importance. 

The  cellular  changes  in  epidemic  meningitis  are  characterized  by  the 
presence  of  polymorphonuclear  leucocytes  in  the  cerebro-spinal  fluid, 
often  in  enormous  numbers.     The  lymphocyte  content  is  also  increased, 


IX]  The  Cerebrospinal  Fluid  113 

but  to  an  extent  that  is  comparatively  so  small  that  it  is  swamped  by 
the  increase  of  polymorphonuclear  cells.  An  absolute  count  of  the 
numbers  of  cells  in  the  fluid  can  be  carried  out  by  the  ordinary  haemo- 
cytometer,  but  is  of  relatively  little  importance,  for  the  macroscopic  sedi- 
mentation on  standing  gives  a  comparative  guide  to  the  total  number  of 
cells  present.  A  differential  count  is  of  much  more  importance.  The 
relative  proportions  usually  shew  a  great  predominance  of  polymorpho- 
nuclear cells,  which  form  80  to  100  per  cent,  of  the  total.  In  the  very 
early  stages,  and  in  the  later  ones  when  hydrocephalus  has  developed,  this 
rule  does  not  hold  good.  In  the  very  early  stages  Netter,  Sophian  and 
others  have  occasionally  found  lymphocytes  forming  more  than  50  per 
cent,  of  the  total;  and  in  fulminating  cases  these  may  reach  a  proportion 
nearly  as  high.  Plate  XI,  fig.  2  is  taken  from  a  film  of  a  fulminating 
case,  the  lymphocytes  here  formed  over  30  per  cent,  of  the  cells  present. 
In  this  type  the  predominance  of  lymphocytes,  or  rather  the  lack  of 
polymorphonuclear  cells,  is  accompanied  by  the  presence  of  very  large 
numbers  of  meningococci.  In  the  chronic  forms,  with  the  absolute 
diminution  in  the  number  of  cells  present,  a  relative  diminution  of 
polymorphonuclear  cells  also  takes  place,  and  the  lymphocytes  relatively 
increase,  even  reaching  as  high  as  70  to  80  per  cent.  The  cytological 
picture  at  this  stage  in  some  cases  thus  closely  resembles  that  of  tuber- 
cular meningitis.  A  purulent  condition  of  the  cerebro-spinal  fluid  occxirs 
in  many  other  diseases -besides  epidemic  meningitis.  It  is  not  therefore 
in  itself  in  any  way  absolutely  diagnostic. 

The  determination  of  the  presence  of  the  meningococcus  in  the 
cerebro-spinal  fluid  has  already  been  dwelt  upon;  and  its  complete 
identification  by  the  testing  of  its  properties,  when  grown  in  pure 
culture,  has  been  stated  to  be  essential  for  a  complete  diagnosis.  It  is 
true  that  considerable  reliance  can  be  placed  upon  the  finding  of  intra- 
cellular diplococci  in  films  of  the  fluid;  but  certain  fallacies  are  liable 
to  crop  up  in  this  procedure,  whereas  a  successful  culture  provides 
a  mass  of  the  organism,  which  can  be  identified  with  certainty  and 
thoroughly  dealt  with.  The  examination  of  films  wiU  be  first  discussed 
and  then  the  best  methods  of  obtaining  a  culture.  Finally  the 
importance  of  the  variations  in  the  numbers  of  meningococci  present 
and  in  their  power  of  growth  will  be  considered.  Films  can  be  made 
directly  from  the  fluid  as  soon  as  possible  after  puncture,  so  as  to 
obtain  a  rough  estimate  of  the  number  of  cocci  and  cells  present. 
If,  however,  the  fluid  is  only  moderately  opalescent,  a  few  cubic 
centimetres  can  be  centrifugahzed,  and  a  concentrated  deposit  obtained 


114  The  Cerebrospinal  Fluid  [CH. 

from  which  films  can  be  made.  The  latter  procedure  is  in  most 
cases  a  preferable  one,  as  by  it  a  large  number  of  leucocytes  are 
obtained  in  any  particular  field,  and  the  labour  of  hunting  for  the 
meningococcus  is  greatly  diminished.  The  number  of  cells  which 
contain  cocci  are  often  very  few,  and  even  in  a  centrifugalized  deposit 
many  fields  may  have  to  be  examined  before  a  single  pair  is  met  with. 
The  most  satisfactory  method  of  staining,  in  order  to  ascertain  the 
presence  of  the  meningococcus,  is  by  means  of  methylene  blue.  The 
film  can  either  be  made  direct  on  the  slide,  allowed  to  dry,  fixed  in 
a  flame,  stained,  washed  and  dried  with  blotting  paper,  and  then 
examined  direct  with  an  oil  immersion  lens;  or,  preferably,  a  film  is 
made  on  a  cover  shp,  fixed  and  stained,  then  washed  in  water  and  the 
cover  slip  inverted  on  the  slide.  Excess  water  is  blotted  oS  and  the 
preparation  is  then  examined  with  an  oil  immersion  lens.  By  this 
latter  method  the  cells  are  better  preserved,  and  it  is  easier  to  make 
certain  that  micrococci,  and  not  particles  of  nuclear  material,  stain 
deposit  or  dust,  are  being  looked  at.  When  the  cocci  are  scanty,  as 
is  frequently  the  case,  it  is  often  a  matter  of  difficulty  to  decide  whether 
they  are  really  present  or  not.  This  difficulty  of  identification  is 
increased  when  Gram's  method  of  staining  is  used.  It  is  fairly  easy 
by  this  method  to  make  certain  of  the  presence  of  an  organism  which 
is  gram-positive,  as  the  rest  of  the  film  is  gram- negative.  But  when 
a  gram-negative  organism  is  being  sought  for,  which  is  only  present 
in  extremely  scanty  numbers,  there  is  a  great  hkehhood  of  error  in 
identification.  The  method  of  staining  also  in  itself  frequently  in- 
troduces extraneous  particles.  It  is  often  therefore  difiicult  to  be 
absolutely  certain  that  an  organism  found  in  a  methylene  blue  pre- 
paration is  definitely  gram-negative  in  a  corresponding  film.  Another 
method  of  identification  by  film  preparations  is  often  very  useful. 
The  cerebro-spinal  fluid  is  placed  in  a  37°  incubator  over-night, 
so  that  whatever  pus  is  present  settles  to  the  bottom.  At  the 
same  time  the  freshly  withdrawn  fluid  acts  as  a  culture  medium  and 
the  meningococci  increase  very  greatly  in  numbers.  A  film,  made 
from  the  sediment  on  the  next  day,  frequently  shews  the  presence  of 
meningococci  in  considerable  numbers,  in  cases  where  none  were  to  be 
identified  with  certainty  in  the  freshly  withdrawn  fluid.  For  the 
examination  of  cells  or  for  the  determination  whether  organisms  are 
intracellular  or  extracellular,  the  incubated  flmd  is  of  course  useless: 
not  only  have  many  cells  degenerated,  but  also,  if  any  considerable 
prohferation    has    taken    place,    cocci    are    now   mainly   extracellular. 


ix]  The  Cerebrospinal  Fluid  115 

The  application  of  gram-stain  can  usually  be  satisfactorily  accom- 
plished. 

The  number  of  cocci  found  in  any  particular  case  varies  considerably : 
as  has  already  been  stated,  in  many  cases  they  are  comparatively  difficult 
to  find  and  are  always  intracellular  when  found.  In  fulminating  cases, 
such  as  that  from  which  the  film  shewn  in  Plate  XI,  fig.  2  was  drawn, 
meningococci  may  be  present  in  very  large  numbers ;  the  great  majority 
are  intracellular,  but  extracellular  forms  are  also  seen  in  every  field. 
The  cocci  appear  in  pairs,  or  more  rarely  in  tetrads,  they  often  vary 
in  size  and  in  staining  power.  The  view  has  been  expressed  that  the 
viabihty  of  an  organism  is  comparable  to  its  staining  capacity ;  arguments 
will  however  be  brought  forward  in  the  chapter  on  the  gram-negative 
cocci,  which  throw  doubt  on  the  truth  of  this  statement.  In  the 
acute  type,  whether  response  to  treatment  occurs  or  not,  intracellular 
cocci  are  in  most  cases  to  be  found:  it  is  on  the  whole  true  that  the 
severity  of  the  disease  corresponds  to  the  number  present.  If  they 
are  easily  to  be  found  in  a  single  field,  the  outlook  is  grave  but  not 
necessarily  hopeless.  The  presence  of  extracellular  cocci  is  even  more 
definitely  a  sign  of  an  extremely  severe  case  in  which  recovery  is  very 
doubtful.  In  the  suppurative  type,  in  which  the  amount  of  pus  pro- 
gressively increases,  the  number  of  cocci  also  increases,  and  in  the  later 
stages  extracellular  cocci  are  present.  In  chronic  conditions  cocci  are 
usually  intracellular  and  are  often  extremely  difficult  to  find.  The 
severity  of  any  particular  case  can  thus  to  some  extent  be  estimated 
by  the  number  of  cocci  found  in  the  cerebro-spinal  fluid.  The  course 
of  a  case  also  roughly  coincides  with  the  number  of  cocci  found:  an 
increase  of  cocci  accompanies  increasing  severity  of  the  disease,  whereas 
with  improvement  the  number  progressively  diminishes.  The  adminis- 
tration of  serum  is  stated  markedly  to  diminish  the  number  of  cocci 
found :  this  is  equally  true  with  treatment  by  lumbar  puncture  alone 
as  in  a  favourable  case  the  numbers  rapidly  diminish.  In  certain  cases, 
such  as  those  of  the  acute  fatal  or  the  suppurative  type,  neither  lumbar 
puncture  alone  nor  the  injection  of  serum  effects  any  reduction  in 
numbers.  The  rapid  removal  of  the  meningococcus  from  the  cerebro- 
spinal fluid  is  certainly  not  yet  proved  to  be  due  to  the  administration 
of  serum. 

The  culture  of  the  meningococcus  from  the  cerebro-spinal  fluid  is 
in  many  cases  easy,  especially  in  the  acute  stages,  provided  that  the 
fluid  can  be  sown  soon  after  removal.  Occasionally,  however,  a  case 
is  met  with,  in  which  cultures  persistently  refuse  to  grow  although  the 


116  The  Cerebro -spinal  Fluid  [oh. 

cocci  can  be  seen  in  films.  In  any  case  special  media  have  to  be  used, 
which  will  be  more  fully  discussed  in  the  final  chapter.  One  medium 
is  pre-eminently  the  best  for  culture  of  the  cerebro-spinal  fluid,  namely 
blood  agar.  We  have  frequently  grown  the  meningococcus  from  the 
cerebro-spinal  fluid  quite  freely  on  blood  agar,  when  other  media  such 
as  nasgar  and  legumin  agar  have  failed  to  grow  it.  It  is  often  possible 
to  cultivate  successfully  a  fluid  which  has  been  incubated  over-night, 
when  no  culture  has  been  obtained  from  the  original  sowing.  The 
procedure  that  we  adopt  is  therefore  as  follows.  When  the  fluid  is 
first  obtained,  one  or  two  loop-fulls  are  sown  on  a  blood  agar  slope, 
a  second  slope  is  also  inoculated  with  |  to  1  c.c.  of  the  fluid.  The 
rest  is  allowed  to  stand  in  the  incubator  over-night.  Next  morning,  if 
no  good  growth  is  shewing  on  the  inoculated  tubes,  the  sediment  at  the 
bottom  of  the  incubated  fluid  is  again  sown  in  similar  amounts  on  two 
other  tubes.  The  tubes  are  examined  daily  and,  if  no  growth  is  shewing, 
the  slope  is  re-inoculated  with  the  condensation  fluid.  The  tubes  are 
kept  for  at  least  five  days,  as  we  have  ultimately  obtained  growth  on 
the  fourth  or  even  fifth  day  in  a  number  of  cases.  In  the  acute  cases 
which  have  terminated  fatally,  growth  has  always  been  easy  to  obtain. 
In  some  severe  cases  which  have  recovered,  as  well  as  in  some  compara- 
tively shght  cases,  culture  has  been  difficult.  In  one  case,  which  was 
punctured  repeatedly,  and  in  which  meningococci  were  found  in  film, 
no  growth  could  ever  be  obtained  either  on  nasgar  or  blood  agar  made 
with  rabbit's  blood.  A  successful  culture  was  however  ultimately 
obtained  on  a  medium  made  with  goat's  blood.  The  strain  thus 
obtained  sub-cultured  on  nasgar,  and  was  kept  ahve  for  some  time. 
By  the  method  just  described  we  have  ultimately  managed  to  grow 
the  meningococcus  from  all  cases  in  which  cocci  could  be  found  in 
films.  A  few  mild  cases,  which  exhibited  practically  all  the  chnical 
signs  of  the  disease  and  completely  recovered,  never  shewed  meningo- 
cocci either  in  film  or  culture.  Polymorphonuclear  cells  were  however 
present  in  the  cerebro-spinal  fluid  in  considerable  numbers,  shewing  that 
a  purulent  infection  of  the  cerebro-spinal  system  was  present.  As 
infection  by  the  meningococcus  is  practically  the  only  purulent  infection 
from  which  recovery  takes  place,  it  is  justifiable  to  conclude  that  these 
were  cases  of  epidemic  meningitis,  in  which  the  meningococcus  could  not 
be  obtained.  In  the  chronic  hydrocephaUc  stages  of  the  disease,  the 
method  of  incubating  the  cerebro-spinal  fluid  will  often  give  a  positive 
culture  though  the  fluid  has  very  little  sediment.  In  some  chronic  cases, 
however,  the  fluid,  though  in  excess,  is  apparently  normal  and  sterile. 


ix]  The  Cerehro-sjnnal  Fluid  117 

In  ttese  cases  intraventricular  puncture  is  stated  sometimes  to  yield  a 
positive  culture,  when  the  lumbar  puncture  fluid  is  sterile.  Failure  to 
obtain  the  meningococcus  either  in  film  or  culture  does  not  necessarily 
mean  that  the  growth  of  the  meningococcus  has  ceased.  The  main  seat 
of  the  infection  is  the  endothehal  fining  of  the  perivascular  spaces  around 
the  cerebral  vessels,  as  they  pass  through  the  sub-arachnoid  space 
(Plate  XI,  fig.  1).  The  cocci  fotmd  in  fluid  withdrawn  by  lumbar  puncture 
are  only  those  that  have  escaped  from  the  chief  point  of  invasion.  It 
is  therefore  quite  possible  for  the  main  focus  to  be  still  active,  though 
the  leakage  into  the  cerebro-spinal  fluid  may  consist  of  only  a  very  few 
degenerate  cocci.  The  preponderance  of  the  intracellular  position 
shews  that  the  escaped  cocci  are  rapidly  taken  up  by  polymorphonuclear 
leucocytes,  a  reaction  which  is  very  characteristic  of  the  whole  group 
of  gram-negative  diplococci.  The  growth  of  a  particular  fluid  therefore 
depends  upon  the  results  of  the  mutual  struggle  between  the  leucocytes 
and  the  cocci. 

The  culture  of  the  meningococcus  from  the  blood  has  been  attempted 
by  various  observers  with  varying  degrees  of  success.  As  already  stated, 
Elser  and  Huntoon  were  able  to  grow  it  in  eleven  cases  out  of  a  series 
of  forty-one.  In  only  one  out  of  four  of  these  was  a  subsequent  attempt 
a  few  days  later  successful.  They  conclude  that  the  appearance  of  the 
organism  in  the  blood  is  a  transient  phenomenon  only.  The  evidence 
is  thus  at  present  doubtful  whether  a  true  septicaemia  is  present  even 
in  the  early  stages  of  the  disease.  A  positive  culture  can  only  be 
obtained  by  using  large  quantities  of  blood,  5  c.c.  or  more ;  the  organisms 
are  thus  present  in  only  very  scanty  numbers.  It  is  quite  possible 
that  the  intense  infection  of  the  central  nervous  system  may  give  rise 
to  a  leakage  of  the  infective  agent  into  the  blood  which  is  transient  in 
nature.  The  presence  of  the  organism  in  the  blood  in  such  small 
numbers  is  not  a  proof  that  the  blood  is  the  primary  path  of  infection. 
Even  in  fulminating  cases,  in  which  the  total  illness  lasts  36  hours  or 
less,  an  intense  infection  of  the  cerebro-spinal  system  is  already  present, 
for  lumbar  pimcture  yields  a  fluid  in  which  large  numbers  of  meningo- 
cocci can  be  found  in  film  preparations.  We  have  attempted  to  cultivate 
the  blood  in  one  such  case  with  entirely  negative  results.  Cases  of  true 
meningococcal  septicaemia  have  been  described  by  Andrewes,  Netter 
and  others.  In  such  cases  the  involvement  of  the  central  nervous 
system  has  been  sfight  or  absent.  Sophian  describes  an  "  accumulative  " 
stage  of  the  disease  with  symptoms  similar  to  influenza,  and  maintains 
that  a  "  bacteremia  "  is  present  in  this  stage ;  he  however  gives  fittle 


118  The  Cerebrospinal  Fluid  [ch.  ix 

direct  proof  of  this;  two  of  the  three  cases  he  quotes  yielded  positive 
results  at  the  first  lumbar  puncture.  The  view  that  the  invasion 
is  primarily  in  the  blood  still  requires  substantiation. 

Sophian  also  maintains  that  in  his  "  accumulative"  stage  meningococci 
may  be  present  in  the  urine,  and  quotes  a  case  in  which  meningococci 
were  recovered.  He  also  states  that  in  the  acute  stage  meningococci 
are  often  found.  We  have  studied  this  question  in  a  certain  number 
of  cases  but  have  been  unable  to  confirm  this.  A  serious  difficulty 
arises  in  that,  in  the  acute  stage,  retention  of  urine  and  even  incon- 
tinence are  the  rule,  a  condition  which  gives  every  facihty  for  various 
infections  of  the  urine  to  occur.  Our  experience  in  attempting  to 
cultivate  catheter  specimens  is  that,  though  large  numbers  of  organisms 
of  various  kinds  can  frequently  be  grown,  meningococci  are  usually 
conspicuously  absent.  We  are  at  any  rate  convinced  that  the  successful 
isolation  of  the  meningococcus  from  the  urine  is  a  matter  of  such 
considerable  difficulty  as  to  be  of  httle  value  for  diagnosis.  Even  if 
a  culture  of  a  gram-negative  diplococcus  is  successfully  obtained,  it 
must  always  be  borne  in  mind  that  another  organism  of  this  kind 
exists  whose  common  location  is  the  genito -urinary  tract,  namely  the 
gonococcus.  The  differentiation  of  the  meningococcus  and  the  gono- 
coccus  is  not  at  all  an  easy  matter,  and  unless  complete  proof  is  given 
that  this  difficulty  has  been  borne  in  mind,  and  the  differential  diagnosis 
between  these  organisms  satisfactorily  carried  out,  any  statement  that 
the  meningococcus  has  been  recovered  from  the  urine,  or  from  any 
region  in  the  genito-urinary  tract,  must  be  accepted  with  caution. 


CHAPTER   X 

EPIDEMIOLOGY 

Contagion  direct  from  throat  to  throat,  frequency  of  gram-negative 
diplococci  in  the  posterior  pharynx.  Variations  in  percentage  of 
meningococcus  carriers,  percentage  in  a  normal  community,  contacts, 
carriers,  temporary  and  prolonged.  Catarrhal  stage  unproven,  sporadic 
distribution  of  cases,  convalescent  cases  as  carriers.  Epidemic  con- 
ditions, susceptibility  of  the  individual,  influenced  by  overcrowding, 
previous  illness,  weather  conditions,  altered  environment,  age,  fatigue. 
Seasonal  distribution,  effect  of  rapid  variation  of  temperature. 
Preventive  treatment  of  cases,  nursing  precautions,  method  of  dealing 
with  contacts  in  search  for  carriers,  procedure  of  taking  swabs  of  the 
postericyr  pharynx,  necessity  of  immediate  sowing,  travelling  incubator. 
Treatment  of  carriers,  isolation,  local  treatment  of  throat  and  nose. 
Conclusions. 

The  cultural  cliaracteristics  of  the  meningococcus  are  such,  that  it 
is  extremely  improbable  that  the  disease  can  be  spread  by  any  other 
method  than  a  direct  one  from  person  to  person.  These  characteristics 
will  be  discussed  fully  in  the  next  chapter,  but  it  may  be  stated  here 
that  the  organism  is  extremely  susceptible  to  drying;  and  can  only 
be  cultivated  on  complex  artificial  media,  just  as  is  the  case  with 
B.  diphtheriae,  the  gonococcus  and  other  organisms,  in  which  direct 
transmission  is  generally  allowed  to  be  the  only  method.  The  meningo- 
coccus has  now  been  recovered  from  the  naso-pharynx  of  the  human 
subject  by  various  observers  in  a  total  of  some  hundreds  of  cases. 
Albrecht  and  Ghon  in  1901  were  the  first  to  demonstrate  its  presence 
in  the  healthy  subject,  though  Kiefer,  Councilman  and  others  had  pre- 
viously found  it  in  the  throats  of  patients  suffering  from  cerebro-spinal 
fever.  On  present  evidence  it  is  therefore  reasonable  to  suppose  that  the 
organism  is  spread  directly  from  throat  to  throat.  The  epidemiology 
of  the  disease  is  thus  primarily  dependent  upon  the  identification 
of  the  meningococcus  in  the  secretions  of  the  nose  and  throat.  This  is 
a  matter  of  considerable  difficulty,  and  is  at  present  still  in  an  almost 
experimental  stage.     For  this  reason  observations  on  the  contacts  of 


120  Epidemiology  [ch. 

any  series  of  cases  of  epidemic  meningitis  vary  greatly  with  regard  to  the 
number  in  which  the  meningococcus  has  been  said  to  have  been  found. 
The  records  of  various  observers  shew  variations  between  30  per  cent, 
or  more,  and  as  low  a  value  as  2  or  3  per  cent.  The  number  of  gram- 
negative  diplococci,  which  are  found  in  the  posterior  pharynx,  is  very 
great,  often  30  to  40  per  cent,  of  persons  in  any  particular  series  will 
be  found  to  harbour  some  form  or  other ;  the  matter  therefore  depends 
entirely  on  the  methods  used  for  the  differentiation  of  such  cocci.  It 
is  doubtless  true  that  the  number  of  positive  contacts  or  carriers  varies 
in  different  outbreaks  to  a  greater  or  less  extent,  according  to  the  hygienic 
conditions  of  the  community  in  which  such  an  outbreak  occurs;  for 
instance,  the  number  is  hkely  to  be  higher  in  the  crowded  community 
of  a  town  than  among  the  scattered  inhabitants  of  a  rural  district; 
but  nevertheless  such  large  variations  cannot  be  explained  entirely  in 
this  way.  The  personal  factor  has  probably  much  more  to  do  with  the 
great  variations  of  different  observers;  the  more  completely  and 
rigorously  every  possible  test  is  made  use  of,  the  more  these  other 
organisms  can  be  excluded,  and  the  smaller  the  percentage  of  carriers 
found  becomes.  Where  rigorous  tests  have  been  used,  the  percentage 
is  seldom  higher  than  3  to  5  per  cent. 

Not  only  have  considerable  numbers  of  observations  now  been 
made  on  the  contacts  of  actual  cases  of  cerebro-spinal  fever,  but  also 
a  number  of  series  of  observations  have  been  carried  out  on  normal 
individuals,  in  communities  where  no  cases  of  meningitis  had  occurred. 
The  largest  series  examined  was  that  of  9000  men,  who  formed  the 
garrison  at  Munich  in  1910,  by  Mayer,  Waldmann,  Fiirst,  and  Griiber. 
They  found  that  about  2  per  cent,  of  these  men  were  meningococcus 
carriers.  No  cases  had  occurred  at  all  recently  in  the  garrison  when 
this  examination  was  carried  out.  It  must,  however,  be  stated  that 
the  garrison  had  had  a  few  cases  each  year,  in  the  two  years  previously, 
so  that  this  community  can  hardly  be  taken  to  be  one  entirely  free 
from  the  disease.  If  it  is  allowed  that  posterior  basic  meningitis  is  a 
sporadic  form  of  epidemic  meningitis,  the  same  criticism  would  however 
apply  to  the  population  of  most  large  towns ;  in  London,  for  instance, 
a  certain  number  of  cases  of  this  disease  of  infants  occur  annually. 
It  seems  fair  therefore  to  take  the  Munich  garrison  as  a  fairly  normal 
community,  and  to  conclude  that  carriers  of  the  meningococcus  do 
exist  in  an  apparently  unaffected  population. 

A  question  of  practical  importance  is  to  define  what  degree  of  con- 
tiguity with  any  particular  patient  should  be  taken  as  constituting 


x]  Epidemiology  121 

"contact."  On  the  hypothesis  that  the  infection  can  only  be  conveyed 
from  throat  to  throat,  it  is  fairly  safe  to  consider  only  those  persons 
as  "contacts"  who  come  intimately  in  contact  with  the  patient  inside 
a  closed  building.  It  is  extremely  unlikely  that  infection  can  be  con- 
veyed out  of  doors,  short  of  direct  contact,  such  as  kissing.  "Contacts" 
can  therefore  be  taken  to  be  all  those  who  are  members  of  the  same 
family,  who  have  taken  meals  in  the  same  room,  or  who  have  slept  in 
the  same  or  an  adjoining  room.  Infection  is  also  doubtless  conveyed 
in  such  places  as  churches,  schools,  pubhc  houses,  theatres,  concert- 
halls,  etc.,  where  large  numbers  of  people  assemble  together.  But  it 
hardly  comes  within  the  range  of  practical  pohtics  to  endeavour  to 
trace  the  spread  of  infection  under  such  circumstances. 

Carriers  are,  of  course,  persons  who,  though  not  suffering  from  the 
disease,  carry  the  meningococcus  in  their  throats  for  a  shorter  or  longer 
time.  The  length  of  time  during  which  the  meningococcus  can  be 
obtained  from  the  throat  of  any  particular  carrier  varies  greatly,  just 
as  is  the  case  with  B.  diphtheriae.  In  our  experience,  carriers  can  be 
roughly  divided  into  two  main  groups,  transient  and  prolonged.  The 
transient  group  consists  of  contacts  in  whom  at  the  first  examination 
the  meningococcus  is  found,  but  who  at  a  subsequent  examination,  a  week 
or  ten  days  later,  prove  to  be  negative,  and  remain  negative  at  further 
examinations.  We  have  tested  such  a  case  for  as  long  as  a  month 
after  the  first  positive  swabbing,  and  still  obtained  a  negative  result. 
It  is  probable,  therefore,  that  such  carriers  are  only  transiently  infected 
and  soon  become  free. 

Another  type  of  carrier,  the  prolonged  type,  is  very  difierent.  The 
meningococcus  often  persists  for  months  in  the  throat,  and,  though 
occasionally  disappearing  for  a  short  time,  subsequently  reappears. 
We  have  lately  had  to  deal  with  a  carrier  in  whom  the  meningococcus 
had  been  found  persistently  at  every  examination  for  more  than  six 
months.  These  are  the  carriers  who  are  in  all  probabihty  most 
responsible  for  the  spread  of  the  disease,  as  they  act  as  sources  of 
infection  over  prolonged  periods,  and  can  carry  the  meningococcus 
from  place  to  place.  It  may  also  fairly  be  assumed  that  these  prolonged 
carriers  are  the  principal  agents  in  perpetuating  the  existence  of  the 
organism.  It  is  probably  due  to  carriers  such  as  these  that  the  organism 
is  kept  ahve  from  season  to  season  and  from  epidemic  to  epidemic. 
By  active  treatment  the  meningococcus  can  often  be  temporarily  driven 
away  from  the  posterior  pharynx,  only  to  reappear  as  soon  as  treatment 
is  discontinued.     Some,  at  any  rate,  of  these  prolonged  carriers  are 


1 22  Epidemiology  [ch. 

suffering  from  a  chronic  pathological  condition  in  one  or  more  of  the 
many  sinuses  connected  with  the  nose,  for  instance,  one  of  our  prolonged 
carriers  suffered  from  chronic  middle  ear  disease,  with  an  inflammatory 
condition  in  the  Eustachian  tube.  Embleton  has  also  given  instances 
in  which  the  sphenoidal  sinuses  were  the  source  of  a  constant  meningo- 
coccal infection  of  the  posterior  pharynx;  adenoids  again  may  act 
similarly  as  a  suitable  nidus.  It  is  probable,  therefore,  that  a  large 
percentage  of  these  chronic  carriers  have  some  condition  of  the  kind. 
Both  with  and  without  treatment  the  posterior  pharynx  of  such  carriers 
may  become  temporarily  free  from  infection,  the  period  varying  con- 
siderably. We  have  had  to  deal  with  a  carrier  who  was  positive  for 
over  two  months ;  he  was  then  found  to  be  negative  at  two  successive 
examinations  about  a  fortnight  apart,  but  on  re-examination,  over  two 
months  later,  he  was  again  found  to  be  positive.  It  is  possible  that 
reinfection  had  taken  place,  but  considering  that  the  intermediate 
period  was  from  July  to  September,  a  time  of  year  in  which  cases  of 
cerebro-spinal  fever  very  rarely  occur,  the  more  probable  explanation 
is  that  this  man  was  a  prolonged  carrier  with  a  period  of  absence  of 
infection  of  the  posterior  pharynx.  As  will  be  explained  in  the  next 
chapter,  the  meningococcus,  if  present  in  the  posterior  pharynx,  is 
almost  always  present  in  large  numbers;  it  is  therefore  unhkely  that 
its  presence  could  be  overlooked  at  two  successive  examinations.  It 
is  thus  clear  that  at  least  two  negative  examinations  are  necessary 
before  a  carrier  can  be  considered  free  of  infection,  and  that  these 
examinations  should  be  separated  by  at  least  a  week  or  ten  days. 
The  best  method  of  deahng  with  carriers  is  a  matter  of  considerable 
difficulty,  and  will  be  discussed  at  the  end  of  this  chapter. 

The  view  has  lately  been  advanced  that  an  infection  of  the  throat 
by  the  meningococcus  frequently  gives  rise  to  a  condition  of  catarrh, 
and  that  three  stages  are  frequently  present  in  any  particular  case: 
namely,  a  catarrhal  stage,  a  septicaemic  stage,  and  a  meningeal  stage, 
any  of  which  may  exist  separately,  or  may  be  succeeded  by  the  next. 
The  question  of  the  existence  of  a  septicaemic  stage  has  already  been 
dealt  with  in  the  previous  chapter,  but  the  question  of  a  catarrhal 
stage,  especially  if  this  can  be  the  only  manifestation  of  infection,  is  of 
very  great  importance  from  the  epidemiological  point  of  view.  Such 
cases  would  come  under  the  designation  of  carriers,  a  simple  catarrh 
being  very  unhkely  to  be  recognized  as  a  phase  of  cerebro-spinal  fever. 
During  the  epidemic  in  England  in  the  winter  and  spring  of  1914-15, 
great  stress  was  laid  on  the  existence  of  this  catarrhal  stage  by  Lundie, 


x]  Epidemiology  123 

Thomas,  Fleming  and  Maclagan,  working  among  the  troops  at  Aldershot. 
We  can  only  say  that  such  a  stage,  though  carefully  looked  for,  has 
never  been  observed  by  us  in  any  of  our  cases;  on  the  contrary,  we 
have  been  struck  by  the  fact  that,  in  every  carrier  identified  by  us, 
not  the  shghtest  sign  of  catarrh  has  been  present.  During  the  course 
of  our  investigations  a  considerable  number  of  contacts  have  been 
examined,  who  suffered  at  the  time  of  examination  with  some  degree 
of  catarrh  of  the  naso-pharynx.  In  none  of  these  was  the  meningo- 
coccus obtained.  The  micrococcus  catarrhalis  was,  however,  present  in 
a  fair  number.  It  seems  to  us,  therefore,  conceivable  that  some,  at 
any  rate,  of  the  cases  of  catarrh,  recorded  as  being  due  to  the  meningo- 
coccus, were  in  reahty  due  to  the  micrococcus  catarrhaUs.  The 
differentiation  of  the  two  organisms  is  difficult,  and  in  our  hands  one 
test,  which  is  said  to  be  reliable,  has  failed,  namely,  the  power  of  growth 
at  23°  C,  for  we  find  that  certain  examples  of  micrococcus  catarrhahs 
do  not  grow  any  better  at  this  temperature  than  the  meningococcus. 
In  view  of  the  difficulties  of  differentiation  of  these  organisms,  we  are 
incUned  to  doubt  the  existence  of  a  catarrhal  stage  in  infections  by  the 
meningococcus,  and  also  to  doubt  that  the  predominance  of  catarrh 
has  any  relationship  to  the  spread  of  infection  by  this  organism.  As 
has  been  already  stated,  in  our  experience  the  throat  of  a  meningo- 
coccus carrier  shews  no  sign  of  any  inflammatory  change.  It  may  here 
be  noted  that  there  is. a  wide  variation  in  the  appearance  of  the  normal 
throat  in  different  individuals,  a  red  throat  is  not  necessarily  an  inflamed 
throat. 

In  studying  an  epidemic  of  cerebro-spinal  fever,  a  striking  fact  is 
the  disconnected  way  in  which  the  bulk  of  the  cases  occur ;  for  example, 
in  the  six  counties  with  which  we  had  to  deal  in  the  winter  and  spring, 
1914-15,  in  no  less  than  twelve  locahties  only  one  case  occurred;  in 
three  only  two  cases  occurred;  in  the  larger  towns,  in  which  there 
were  a  number  of  cases,  these  were  scattered  irregularly  over  three  or 
four  months,  and  there  was  httle  apparent  connection  between  them. 
It  is  true  that  we  only  dealt  with  cases  occurring  among  troops,  but  in 
the  civilian  population  the  number  and  distribution  of  cases  was  almost 
identical.  Even  in  a  so-called  epidemic,  therefore,  the  disease  tends  to 
appear  in  a  sporadic  fashion.  Bolduan  and  Goodwin  found  that,  out  of 
1500  cases  in  the  New  York  epidemic  of  1904-5,  there  were  only  fifty-eight 
instances  of  more  than  one  case  in  a  house,  and  in  only  nineteen  of  these  did 
more  than  two  cases  occur.  It  appears,  therefore,  that  only  a  very  small 
percentage  of  those  who  run  the  risk  of  infection  ever  contract  the  disease. 


124  Epidemiology  [ch. 

It  is  also  insisted  upon  by  many  observers  that  the  number  of  carriers 
found  usually  greatly  exceed  the  number  of  cases ;  it  would  follow  that 
the  majority  of  normal  individuals  are  insusceptible  to  the  disease,  but 
may  be  at  some  time  or  other  carriers  of  the  meningococcus.  If  this 
is  so,  it  would  explain  the  sporadic  occurrence  of  cases  in  an  epidemic. 
A  considerable  increase  in  the  number  of  carriers  would  expose  many 
more  persons  to  the  risk  of  infection,  and  the  comparatively  few,  who 
were  susceptible  to  the  disease,  would  be  more  exposed  to  the  risk  of 
contracting  it.  Such  persons  being  comparatively  few  the  disease 
would  then  appear  in  a  sporadic  manner.  The  disease  need  not  be 
carried  from  one  patient  to  another  by  means  of  one  single  carrier,  but 
many  intermediate  carriers  may  be  concerned  in  such  a  transmission. 
If  some  of  these  intermediate  carriers  were  of  the  transient  type,  the 
tracing  of  the  path  of  infection  would  become  impossible. 

Though,  as  has  just  been  argued,  it  is  probable  that  the  infection 
is  spread  from  case  to  case  by  means  of  one  or  more  carriers,  a  number 
of  instances  of  direct  infection  have  been  recorded.  In  the  meningitis 
hospital  at  Dallas,  U.S.A.  in  1912,  fourteen  cases  occurred  amongst 
those  in  attendance  on  patients,  and  in  thirty-two  of  the  cases  described 
by  Bolduan  in  the  New  York  epidemic  of  1904-5  direct  infection  can 
be  presumed ;  there  are  numerous  other  recorded  instances.  It  must 
also  be  recognised  that  a  convalescent  from  the  disease  may  act  as 
a  carrier.  We  have  ourselves  met  with  a  few  instances  in  which, 
though  complete  recovery  had  taken  place,  the  meningococcus  was 
still  present  in  the  naso-pharynx.  We  have  obtained  identical  cultural 
and  serum  reactions  from  the  strains  then  isolated,  and  from  the  original 
strain  obtained  by  lumbar  puncture.  The  presence  of  the  organism  in 
the  throat  of  cases  has  been  studied  by  von  Lingelsheim,  Netter  and 
Debre,  and  Goodwin  and  ShoUy,  at  various  stages  of  the  disease. 
They  find  that  the  organism  is  present  in  about  60  per  cent,  of  cases 
during  the  first  week,  that  the  number  progressively  dinunishes,  but 
Goodwin  and  Sholly  still  found  the  organism  present  in  6  per  cent, 
after  the  second  month.  In  one  of  our  own  cases,  in  which  the  illness 
ran  a  course  of  three  and  a  half  weeks,  positive  cultures  were  obtained 
from  the  naso-pharynx  at  every  examination  for  as  long  as  four  months 
after  the  initial  attack.  Goodwin  and  Sholly's  figures  shew  that  such 
an  occurrence  fortunately  is  comparatively  uncommon,  and  that  in 
most  cases  of  the  disease  the  infection  of  the  naso-pharynx  disappears 
with  convalescence.  It  is,  however,  of  the  utmost  importance  that  the 
naso-pharynx  of  all  convalescents  should  be  thoroughly  examined,  and 


x]  Epidemiology  125 

that,  if  the  meningococcus  is  found,  they  should  be  treated  just  hke 
other  carriers. 

The  conditions  under  which  the  disease  becomes  epidemic  are  at 
present  puzzling,  but  two  types  of  community  appear  to  be  especially 
susceptible  to  such  outbreaks,  namely,  children  in  crowded  town  areas, 
and  troops.  In  England  epidemics  of  the  disease  had  been  practically 
imknown  before  the  winter  1914-15,  though,  as  has  already  been 
stated,  sporadic  cases  of  posterior  basic  meningitis  are  always  present 
in  large  towns.  In  Belfast,  however,  the  disease  has  been  prevalent 
for  some  years  past.  Dublin,  on  the  other  hand,  where  overcrowding 
in  the  poor  district  is  worse  than  in  Belfast,  has  escaped.  Our  know- 
ledge of  the  disease  has  been  greatly  increased  of  late  years  by  the  work 
done  in  New  York.  There  the  disease  is  always  prevalent  to  some 
extent  every  year,  but  in  the  winter  and  spring  of  1904,  1905  and  1906, 
a  severe  epidemic  occurred,  the  numbers  rising  from  about  200  in  1903 
to  2700  in  1905.  Since  then  a  progressive  diminution  has  taken  place, 
only  250  cases  being  recorded  in  1912.  The  disease  has  chiefly  occurred 
in  the  poor  districts,  into  which  a  constant  stream  of  immigrants  takes 
place  from  all  over  Europe;  the  population  is  therefore  continuoxisly 
changing,  a  factor  which  may  be  of  considerable  importance.  The 
outbreak  in  England  of  1914-15  primarily  took  place  among  troops, 
and  more  especially  among  newly-formed  units.  The  amount  of 
shifting  of  the  population  which  took  place  with  the  formation  of  the 
new  armies  was  very  great,  and  this  was  probably  of  great  importance 
in  bringing  about  the  epidemic.  The  occurrence  of  epidemics,  when 
the  population  is  rapidly  changing,  would  agree  with  the  view  already 
expressed  that  there  probably  exist  a  certain  number  of  carriers  in 
most  civihzed  communities,  that  only  a  small  proportion  of  the  popula- 
tion is  susceptible,  and  that  to  produce  an  epidemic  it  is  necessary 
to  bring  susceptible  individuals  and  carriers  into  fairly  intimate  contact. 
Another  type  of  community  also  is  hable  to  epidemics,  the  conscript 
armies  of  the  continent.  Here  again  large  numbers  of  individuals  are 
collected  together  from  varying  sources,  and  become  freely  and  closely 
intermingled  so  that  the  same  conditions  occur,  namely,  a  commimity 
which  is  rapidly  changing. 

The  susceptibihty  of  any  particular  individual  can,  in  all  probabihty, 
vary  considerably  according  to  the  conditions  of  the  individual;  so 
that  it  is  not  merely  a  question  of  exposing  susceptible  persons  to 
infection,  but  also  of  producing  conditions  in  which  individual  suscepti- 
bility is  raised.     The  formation  of  the  new  armies  in  England  was 


LIBRARY  OF  TKE 

ALUMNf  ASSOC! ATIOMr 

C0LLE6E-    -  .^GEOM 


126  Epidemiology  [ch. 

accomplished  at  very  high  pressure,  and  the  conditions  of  housing, 
clothing,  etc.,  had  to  be  carried  out  in  the  best  manner  available, 
buildings  but  ill  adapted  to  the  housing  of  troops  having  to  be  temporarily 
used.  Such  conditions  probably  had  considerable  influence  in  bringing 
about  the  outbreak.  The  influence  of  various  factors  will  now  be  dis- 
cussed and  particularly  their  effect  on  the  lowering  of  resistance  to  the 
disease.  The  most  important  factor  in  bringing  about  the  spread  of  the 
disease  is  overcrowding;  this  is  shewn  by  the  localities  in  which  out- 
breaks occur.  They  occur  either  in  overcrowded  slum  areas  of  large 
towns,  or  among  troops  crowded  together  in  barracks  or  billets.  In 
England  during  the  winter  of  1914-15,  the  population  of  certain  small 
towns  in  the  Eastern  counties  was  nearly  doubled  by  the  influx  of 
troops,  who  were  accommodated  to  a  greater  or  less  extent  by  billeting 
on  the  population.  The  normal  conditions  of  space  and  ventilation 
were,  therefore,  "entirely  altered.  Troops  were  billeted  in  buildings 
which  were  not  constructed  to  be  used  for  sleeping  purposes,  and  in 
which  it  was  extremely  difficult  to  secure  adequate  ventilation,  even 
though  the  cubic  content  was  adequate;  conditions  of  overcrowding 
and  inadequate  ventilation  were  therefore  common. 

In  our  experience  it  is  not  uncommon  to  find  that  some  compara- 
tively slight  illness  has  preceded  the  acute  onset  of  cerebro-spinal 
fever,  such  as  influenza,  or  sore  throat.  Seeing  that  in  such  cases  the 
patient  was  often  well  enough  to  be  sent  home  from  hospital  on  leave 
before  the  acute  onset  of  meningitis,  we  do  not  hold  the  view  that 
such  illnesses  were  really  an  early  stage  of  a  meningococcus  infection; 
again  we  have  never  found  a  severe  catarrh  associated  with  the  presence 
of  the  meningococcus  in  the  naso-pharynx.  We  therefore  hold  that 
these  previous  illnesses  were  correctly  diagnosed,  and  that  the  true 
reading  of  the  matter  is  that  general  diminished  resistance,  brought 
about  by  this  previous  illness,  has  rendered  the  patient  more  susceptible 
to  invasion  by  the  meningococcus.  It  may  be  remarked  that  there  is 
a  strong  probabihty  that  in  some  of  these  cases  infection  took  place 
while  on  leave,  for  in  some  instances  such  a  case  was  the  only  one 
occurring  in  the  station;  the  assumption  is  therefore  reasonable  that 
the  patient  became  exposed  to  infection  in  the  locahty  where  he  went 
on  leave,  and  where  cases  of  the  disease  were  known  to  be  occurring. 

Other  temporary  debihtating  influences  are  seasonal  weather  con- 
ditions, and  inadequate  protection  from  these.  In  the  case  of  the 
newly-raised  armies  in  England  there  was  at  first  considerable  shortage 
of  clothing,  owing  to  the  very  large  numbers  of  men  who  had  to  be  dealt 


x]  Epidemiology  127 

with.  The  winter  was  a  particularly  wet  one,  and  it  thus  occurred 
that  many  of  the  troops  were  unable  to  obtain  a  thorough  change  of 
clothing  as  often  as  would  have  been  desirable.  In  consequence  the 
men  crowded  together  in  their  quarters,  and  were  reluctant  to  allow  of 
sufficient  ventilation  in  them.  Such  conditions  had  the  result  of 
lowering  their  general  resistance,  and  in  some  units  the  size  of  the  sick 
parades  became  very  large.  Similar  conditions  prevail  in  the  winter 
and  spring  in  the  poorer  districts  of  large  cities.  The  children,  often 
ill-clad,  are  out  in  all  weathers,  get  thoroughly  wet  and  then  return 
to  their  crowded  dwelUngs.  Under  such  circumstances  the  suscepti- 
bihty  to  infection  becomes  greatly  increased. 

The  general  nutrition  of  the  individual  does  not  seem  to  be  of  much 
importance  with  regard  to  possibiUty  of  infection;  many  of  our  cases 
have  been  men  in  excellent  condition  and  health  when  suddenly  seized 
by  the  disease.  The  alteration  in  environment  and  acclimatization  to 
an  entirely  new  mode  of  life  may,  however,  have  a  considerable  influence. 
Many  of  the  men,  who  joined  the  army  in  England,  had  been  accustomed 
to  an  entirely  difierent  mode  of  existence,  and  those  who  had  been  taken 
from  sedentary  occupations  indoors  would  take  some  time  to  become 
used  to  their  new  conditions.  The  number  of  cases,  that  occurred  in 
our  district  in  men  of  under  four  months'  service,  was  not  out  of  pro- 
portion to  the  number  of  those  who  had  six  to  nine  months',  but  the 
mortahty  was  much  higher  among  the  recently  joined.  This  may  be 
interpreted  as  an  indication  that  the  resistance  of  the  more  recent 
recruits  was  lower  than  among  those  who  had  become  accustomed  to 
their  new  mode  of  existence,  and  were  better  able  to  look  after  them- 
selves. 

When  an  epidemic  occurs  among  troops,  as  the  greater  number  of 
those  exposed  to  infection  have  hardly  reached  the  adult  stage,  the 
greater  number  of  cases  will  occur  among  the  younger  soldiers ;  and  in 
the  new  army  in  England  the  preponderance  of  young  men  was  very 
marked.  There  were  therefore  a  larger  number  of  cases  in  men  under 
twenty-one  than  in  those  over  this  age,  but  from  this  it  cannot  be  argued 
that  there  was  any  great  increase  of  susceptibility  at  the  earher  ages. 
We,  however,  found  a  much  higher  mortality  in  those  contracting  the 
disease  who  were  under  twenty-two  years  of  age.  With  regard  to 
epidemics  among  troops,  it  cannot  then  be  said  that  age  is  an  important 
factor,  though  the  outlook  is  perhaps  more  serious  in  a  young  soldier 
recently  joined. 

When  we  turn  to  the  study  of  epidemics  occurring  in  towns  amongst 


128  E2nclemiology  [ch. 

a  civilian  population,  age  is  seen  to  be  an  extremely  important  factor. 
In  the  New  York  epidemic  in  1905,  1906,  1907,  over  65  per  cent,  of 
cases  occurred  in  children  under  ten  years  of  age.  In  the  Prussian 
epidemic  extending  over  the  same  period,  80  per  cent,  of  cases  were 
below  sixteen  years  of  age.  In  some  older  epidemics  recorded,  it  is 
stated  that  adults  were  more  frequently  attacked  than  children,  but 
such  records  are  of  doubtful  value,  as  the  cause  of  the  disease  had  not 
then  been  discovered,  and  an  exact  diagnosis  was  not  possible.  It  must 
also  be  borne  in  mind  that,  owing  to  the  high  rate  of  infant  mortaUty, 
the  cause  of  death  in  children  was  in  those  times  not  a  matter  for  such 
searching  enquiry  as  at  present.  All  recent  records  agree  in  shewing 
that  the  disease  is  one  of  early  life  when  it  attacks  the  general  popula- 
tion. In  the  recent  outbreak  in  England,  the  age  incidence  of  the 
disease  entirely  changed  when  it  spread  from  the  troops  to  the  civilian 
population;  among  the  latter  by  far  the  greater  number  of  cases 
occurred  in  children.  The  conclusion  may  be  drawn  that  the  suscepti- 
bihty  to  the  disease  diminishes  progressively  with  the  increase  of  age. 
The  distribution  of  the  disease  in  its  sporadic  and  mild  form  also  lends 
support  to  this  view ;  for  posterior  basic  meningitis  is  almost  exclusively 
a  disease  of  infants  under  two  years  of  age.  It  follows  from  this  diminu- 
tion of  susceptibihty  with  advance  in  hfe,  that  an  epidemic  attacking  an 
adult  community,  such  as  a  body  of  troops,  must  be  a  very  virulent  one. 
It  has  been  universally  found  that  the  mortahty  in  such  an  outbreak 
is  higher  than  when  a  civihan  population  is  affected ;  Robb  found  in 
Belfast,  during  the  winter  1914-15,  that  the  mortahty  rose,  notwith- 
standing treatment,  as  high  as  36  per  cent.,  though  previously  to  this  it 
had  been  as  low  as  24  per  cent.,  with  the  same  treatment.  The  difference 
can  be  partly  ascribed  to  the  mobilization  of  large  bodies  of  troops. 

It  has  been  suggested  that  fatigue  plays  a  part  in  increasing  the 
susceptibility  to  cerebro-spinal  fever  among  troops.  In  our  experience, 
however,  this  factor  is  not  a  conspicuous  one.  It  is  true  that  the  new 
armies  were  being  trained  at  high  pressure,  but  in  no  case  was  it  clear 
that  a  soldier  had  been  performing  any  specially  fatiguing  work  when 
he  developed  the  disease.  In  a  number  of  cases  the  men  first  became 
seriously  ill  when  performing  mihtary  duties,  but  in  all  these  cases  they 
had  begun  to  feel  unwell  before  the  particular  duties  were  commenced. 
In  some  of  the  most  severe  cases  the  soldier  had  gone  to  bed  apparently 
perfectly  well,  and  had  been  found  severely  ill  or  unconscious  the 
following  morning;  in  one  fulminating  case  the  man  had  gone  to  bed 
in  the  ordinary  way,  and  was  found  dead  in  bed  by  his  comrade  the 


x]  Epidemiology  129 

next  morning.     It  is  therefore  doubtful  whether  excessive  fatigue  plays 
an  important  part  in  the  aetiology  of  the  disease. 

Cerebro-spinal  fever  is  essentially  a  disease  of  winter  and  spring; 
all  recorded  epidemics  have  begun  in  one  of  the  four  months  December 
to  March.  The  epidemic  usually  reaches  its  height  in  spring  from  March 
to  May.  With  the  coming  of  summer,  the  disease  rapidly  decUnes,  and 
has  usually  practically  disappeared  by  the  end  of  July.  It  is  in  most 
cases  a  disease  of  the  temperate  zones,  though  a  few  outbreaks  have 
occurred  in  tropical  regions,  such  as  the  Soudan  and  Bast  Africa.  Sweden 
has  suffered  especially  severely  from  it,  and  outbreaks  have  taken  place 
in  all  countries  of  Europe.  America  has  also  suffered  many  epidemics. 
England,  up  to  the  winter  1914-15,  had  been  remarkably  free  from  the 
disease.  The  weather  in  winter  and  early  spring  in  temperate  chmates  is 
characterised  by  the  occurrence  of  extremely  rapid  daily  variations  in 
temperature,  so  that  it  is  more  difficult  at  this  time  of  year  than  any 
other  for  the  individual  to  adapt  himself  to  the  external  weather  con- 
ditions. Amongst  the  poorer  classes  in  large  cities,  and  amongst 
troops  in  billets  or  temporary  buildings,  this  difficulty  is  increased, 
more  especially  as  the  stock  of  clothing  in  both  cases  is  scanty,  and 
allows  of  httle  change.  This  rapid  variation  of  temperature  seems  to 
be  of  more  importance  than  any  actual  degree  of  cold  or  wet.  There 
is  no  direct  association  between  a  severe  winter  and  the  outbreak  of 
cerebro-spinal  fever ;  on  the  contrary  some  of  the  most  severe  epidemics 
have  occurred  with  a  mild  winter,  as,  for  instance,  was  the  case  in 
England  in  1914-15.  Among  the  cases  with  which  we  had  to  deal  in 
this  outbreak,  there  appeared  to  be  a  certain  relationship  between  a 
rapid  fall  of  the  barometer  and  the  onset  of  the  disease.  The  amount 
of  rainfall,  on  the  other  hand,  did  not  appear  to  be  of  very  great 
importance.  It  therefore  seems  that  the  rapid  changes  of  temperature 
associated  with  high  winds,  which  frequently  occur  in  the  spring,  and 
are  accompanied  by  a  marked  fall  in  the  barometer  without  necessarily 
severe  rainfall,  are  of  more  importance  in  lowering  individual  resistance 
than  the  actual  rainfall.  The  mean  temperature  of  the  surface  of  the 
body  varies  considerably  with  different  seasons  of  the  year,  and  the 
process  of  alteration  of  this  is  a  gradual  one.  Rapid  daily  variations 
of  temperature  may  therefore  have  a  marked  effect  on  an  individual, 
even  though  he  is  accustomed  to  a  large  variation  of  temperature 
between  summer  and  winter  much  greater  than  the  daily  variations 
in  question.  Children,  having  in  proportion  a  much  larger  surface 
relative  to  volume,  are  much  more  susceptible  to  such  changes. 

F.  &Q.  9 


130  Ejjidemiology  [oh. 

The  autumn  of  1914  was  in  England  one  of  the  wettest  on  record, 
but  yet  cerebro-spinal  meningitis  did  not  begin  during  this  period. 
March  and  April,  when  the  epidemic  was  at  its  height,  were  particularly 
dry;  again  the  conditions  under  which  troops  were  hving  were  con- 
siderably better  in  March  and  April  than  in  the  autumn,  when  large 
bodies  of  newly-raised  troops  had  to  be  rapidly  accommodated;  the 
troops  had  also  become  more  acchmatized  to  their  new  conditions  by 
that  time.  If  conditions  produced  by  excessive  rainfall,  such  as  constant 
wettings  and  the  saturation  of  sites  of  temporary  encampments,  were 
the  main  cause  of  the  spread  of  the  disease,  the  epidemic  should  have 
started  in  the  autumn  of  1914  rather  than  the  beginning  of  1915.  The 
conclusion  may  therefore  be  drawn  that  bad  weather  conditions  alone 
are  not  the  chief  predisposing  cause ;  rapid  daily  variations  of  tempera- 
ture, with  or  without  much  rain,  are  of  far  greater  importance. 

The  preceding  arguments  lead  to  the  conclusion  that  the  meningo- 
coccus is  spread  by  being  carried  in  the  nose  and  throat  of  normal 
individuals,  convalescent  patients,  and  patients  actually  suffering  from 
the  disease,  and  is  imparted  to  other  individuals  by  direct  contagion*. 
Such  contagion  takes  place  either  by  absolute  contact  such  as  kissing, 
or  by  the  spraying  of  the  discharges  of  the  nose  and  throat,  as  in 
coughing,  speaking,  singing,  or  snoring.  The  question  of  preventive 
measures  therefore  resolves  itself  into  the  isolation  and  treatment  of 
such  persons.  There  is  also  a  possibility  that  the  organism  might  be 
spread  by  the  contamination  of  articles  of  clothing,  or  of  floors  and 
walls,  by  such  proceedings  as  spitting ;  but,  as  has  already  been  stated, 
the  extreme  susceptibiUty  of  the  meningococcus  to  drying  renders  such 
methods  of  spread  at  least  very  unhkely.  The  fact  that  by  far  the 
greater  number  of  carriers  have  normal  throats  and  therefore  no 
excessive  discharges  from  the  nose  or  posterior  pharynx,  and  thus  Uttle 
inclination  to  indulge  in  spitting,  is  an  additional  factor  in  making  such 
a  method  of  spread  improbable.  The  treatment  of  convalescent  cases,  as 
regards  the  possibihty  of  their  spreading  infection,  is  similar  to  that  of 
carriers.  The  treatment  of  cases  will  be  first  discussed,  and  then  methods 
of  identification  and  treatment  of  carriers,  including  convalescent  cases. 

The  precautions  required  in  treatment  of  cases  are  very  similar  to 
those  needed  in  the  case  of  diphtheria.  The  main  difference  between 
the  two  diseases  is  that,  probably  owing  to  the  absence  of  coughing, 
the  immediate  attendants  undergo  less  risk  in  cerebro-spinal  fever. 
The  necessity  for  a  special  isolation  hospital  is  not  apparent,  so  long 
*  An  example  of  such  a  direct  spread  from  throat  to  throat  is  given  in  Appendix  I. 


x]  Epidemiology  131 

as  conditions  in  the  particular  hospital  are  good.  We  are  very  strongly 
of  opinion  that  the  first  essential,  not  only  from  the  patient's  point  of 
view,  but  also  from  that  of  the  hospital  staff,  is  the  very  greatest  freedom 
of  ventilation,  which  cannot  be  too  excessive.  Our  experience  at  the 
First  Eastern  General  Hospital  at  Cambridge  is  very  striking  from  this 
point  of  view.  The  wards  are  temporary  buildings,  with  the  south 
side  completely  open,  so  that  the  patients  are  nursed  practically  in 
the  open  air.  At  the  beginning  of  the  epidemic  the  earhest  cases  of 
meningitis  were  scattered  through  the  ordinary  wards,  and  no  special 
precautions  of  any  kind  were  taken,  yet  none  of  the  nurses  or  orderhes 
in  attendance  developed  the  disease.  When  in  March  the  number  of  cases 
became  great,  they  were  all  collected  together  at  the  end  of  one  ward ; 
the  rest  of  the  ward  was,  however,  filled  with  other  patients,  the  only 
precaution  taken  being  that  an  empty  bed  was  left  between  the  two 
divisions  of  the  ward.  The  nurses  and  orderhes  were  in  attendance 
on  the  whole  ward,  yet  no  fresh  case  occurred,  either  amongst  the 
other  patients  or  the  nursing  staff.  At  the  height  of  the  epidemic,  when 
up  to  thirty  cases  were  being  treated,  the  whole  ward  was  given  up 
to  the  disease.  Later,  when  the  epidemic  was  decUning  and  the 
number  of  patients  had  diminished,  a  very  thorough  examination  was 
made  of  the  throats  of  all  nurses  and  orderhes  on  duty  in  the  ward. 
In  only  one  case  was  the  meningococcus  present.  This  carrier  had  only 
been  in  the  ward  a  week,  and  was  subsequently  found  six  months  later 
to  be  still  harbouring  the  organism.  He  therefore  belongs  to  the  group 
of  prolonged  carriers,  and  it  is  at  least  questionable  whether  his  throat 
was  first  infected  in  the  ward.  It  appears,  therefore,  that  the  risk  of 
even  harbouring  the  organism  in  the  throat  and  becoming  a  carrier  is 
not  very  great,  either  for  those  in  attendance  on  cases,  or  for  other 
patients  treated  in  the  same  ward,  if  only  very  free  ventilation  is  present. 
The  Uterature  shews  that  the  number  of  nurses  and  medical  attendants 
who  have  contracted  the  disease  is  small.  It  appears,  however,  to  be 
extremely  inadvisable  to  treat  the  disease  in  small  temporary  hospitals 
in  converted  houses,  for  during  the  1914—15  epidemic  in  England, 
under  such  circumstances  cases  of  infection  among  attendants  occurred. 
The  conditions  in  any  particular  hospital  requisite  to  produce  infection 
among  the  hospital  staff  are,  in  fact,  parallel  to  those  already  insisted 
upon,  while  considering  predisposing  causes  of  the  spread  of  the  disease. 
If  the  hospital  is  not  overcrowded,  and  the  freest  ventilation  is  always 
present,  the  risks  to  the  attendants  are  small.  The  treatment  of  cases 
in  either  a  well-ventilated  ward,  or  in  some  temporary  building  with 

9—2 


132  Epidemiology  [ch. 

the  freest  ventilation,  is  advisable  not  only  in  the  interest  of  the  patients 
themselves,  but  also  for  those  in  attendance  on  them. 

The  precautions  that  should  be  taken  in  the  actual  nursing  of 
cerebro-spinal  fever  are  simple,  and  are  mainly  concerned  with  the 
discharges  from  the  nose  and  throat.  Luckily,  as  has  already  been 
mentioned,  the  spread  of  these  discharges  by  coughing  is  unusual,  as 
cough  is  seldom  present.  In  very  severe  cases  the  condition  of  the 
mouth  and  throat  becomes  very  foul,  and  an  escape  of  the  foul  secretion 
at  the  corners  of  the  mouth  sometimes  occurs ;  such  a  discharge  should 
be  carefully  dealt  with  by  disinfection.  The  delirium  in  this  disease 
is  an  active  one  and  the  patients  are  often  extremely  violent  and  noisy ; 
when  such  a  patient  is  shouting  and  throwing  himself  about,  he  is 
doubtless  distributing  meningococci  into  the  surrounding  air.  It  is 
therefore  advisable  that  such  a  patient  should  be  separated  by  a  reason- 
able interval  from  other  patients,  and  that  precautions  should,  as  far  as 
possible,  be  taken  by  those  in  attendance  on  such  a  case,  to  avoid 
directly  exposing  themselves  to  the  patient's  breath  when  in  a  dehrious 
state.  Precautions  should  also  be  taken,  such  as  gargUng  with  a  mild 
antiseptic,  or,  better,  using  a  nasal  douche.  A  hypodermic  injection  of 
morphia  is  of  great  value  in  quieting  the  patient;  not  only  does  it 
have  a  beneficial  effect  by  preventing  exhaustion  and  promoting  sleep, 
but  also  it  is  a  most  reasonable  procedure  to  take  to  lower  the  risk  of 
infection  of  immediate  attendants,  which  is  much  less  when  the  patient 
is  quiet.  All  articles  actually  used  in  treating  the  patient,  such  as 
feeding  utensils  and  linen,  should  be  kept  separate  and  thoroughly 
disinfected.  The  risk  from  discharges  of  the  nose  and  throat  is  pro- 
bably small  if  such  discharges  dry,  but  nevertheless,  it  is  a  reasonable 
precaution  to  disinfect  articles  likely  to  be  soiled  by  them.  Incontinence 
is  also  a  marked  feature  in  all  stages  of  the  disease,  and  whether  the 
view  is  held  or  not  that  the  urine  is  frequently  infected,  it  is  reasonable 
to  disinfect  all  soiled  hnen.  The  disinfection  of  the  urine  is  a  simple 
matter,  and  should  be  carried  out,  though  we  personally  hold  that  no 
reasonable  evidence  has  yet  been  brought  forward  that  infection  of  the 
urine  is  at  all  a  common  occurrence.  The  throats  of  those  who  are 
nursing  cases  during  an  epidemic  should  occasionally  be  examined  to 
see  if  any  are  carriers ;  the  risk  of  the  nurse  infecting  a  patient  suffering 
from  some  other  disease  does  not,  however,  appear  to  be  great  in  a 
well-ventilated  hospital. 

The  discovery  and  treatment  of  carriers  is  an  entirely  different 
problem,  and  is  a  matter  of  difficulty.     Our  own  procedure  has  been 


x]  Epidemiology  133 

to  arrange  that,  directly  a  case  is  suspected  to  be  suiiering  from  cerebro- 
spinal fever,  it  should  be  removed,  and  those  who  may  be  considered 
contacts  should  be  isolated.  On  the  diagnosis  of  the  case  becoming 
confirmed  by  lumbar  puncture,  the  isolated  contacts  all  have  had  their 
throats  swabbed,  and  they  have  been  kept  in  isolation  until  their 
swabs  have  proved  negative.  The  isolation  of  contacts  has  been  carried 
out  either  in  the  house  where  the  case  occurred,  or,  preferably,  in  the 
case  of  billeted  troops,  the  soldiers  have  been  removed  to  some  special 
place  of  isolation.  For  this  purpose  the  local  small-pox  hospital  may 
be  conveniently  utihzed,  or  if  such  is  not  available,  an  unoccupied 
billet  can  be  used,  where  the  accommodation  and  ventilation  are  good. 
The  isolation  enforced  has  not  been  excessively  strict;  contacts  have 
been  allowed  to  go  out  in  the  open  air,  and  very  frequently  to  carry 
on  their  ordinary  duties,  as  long  as  these  were  all  done  in  the  open. 
They  have  not  been  allowed  to  enter  any  closed  building,  and  have 
taken  all  meals  and  slept  at  the  place  of  isolation,  that  is  to  say,  the 
restrictions  put  upon  them  were  that  they  should  not  mingle  with 
others  in  any  closed  place,  in  which  a  possibiUty  of  a  throat  to  throat 
infection  could  occur.  If  the  first  swab  taken  after  removal  of  the 
patient  was  found  to  be  negative,  such  contacts  were  allowed  to  resume 
their  ordinary  life.  If,  however,  a  contact  proved  to  be  a  carrier, 
the  throat  swab  being  positive,  his  isolation  continued,  and  he  was 
further  dealt  with. 

As  the  meningococcus  inhabits  the  posterior  pharynx  in  the  upper 
part  of  the  nose,  it  is  essential  that  the  swab  should  be  taken  from  the 
posterior  wall  of  the  pharynx,  as  far  as  possible  without  contamination 
from  the  tongue,  tonsils,  uvula,  or  pillars  of  the  fauces.  For  this  purpose 
a  form  of  covered  swab  has  been  invented  by  West.  The  swabbing 
wire  is  enclosed  in  a  narrow  glass  tube,  about  nine  inches  long,  the 
terminal  inch  and  a  half  of  which  is  curved;  the  wire  on  which  the 
swab  is  made  is  also  curved  in  the  same  region,  and  consists  in  its 
curved  portion  of  a  flattened  spring,  so  that,  if  the  wire  is  withdrawn 
a  Httle,  the  spring  flattens  out  in  passing  iato  the  straight  portion  of 
the  glass  tube.  When  sterihzed,  the  open  curved  end  of  the  tube  is 
fitted  with  a  cotton-wool  plug.  The  method  of  using  the  swab  is  as 
follows :  the  cotton  wool  plug  is  taken  out  and  the  glass  tube  is  passed 
with  its  curve  lying  in  a  horizontal  plane  down  the  throat  behind  the 
uvula  and  soft  palate.  When  in  position,  the  tube  is  rotated  through 
a  right  angle,  so  that  the  curve  is  now  vertical  and  passes  up  into  the 
posterior  pharynx  behind  the  soft  palate.     The  swabbing-wire  is  now 


134  Epidemiology  [ch. 

pushed  out  beyond  the  end  of  the  tube,  and  the  cotton  wool  at  the  end 
of  it  comes  in  contact  with  the  secretion  of  the  posterior  pharyngeal 
wall.  The  wire  is  again  withdrawn  into  the  tube,  and  the  glass  tube 
is  again  rotated  through  a  right  angle  and  withdrawn  from  the  throat. 
It  is  claimed  that  in  this  manner  an  uncontaminated  sample  of  the 
posterior  pharyngeal  secretion  can  be  obtained.  We  have  tried  this 
method  to  some  considerable  extent,  but  have  come  to  the  conclusion 
that  it  defeats  its  own  object.  The  introduction  of  such  a  large  and 
clumsy  piece  of  apparatus  into  the  throat  causes  a  very  considerable 
flow  of  saUva,  and  by  the  time  that  the  tube  has  been  passed 
and  again  withdrawn  the  amount  of  saliva,  which  collects  round  its 
open  end,  is  very  considerable.  Not  only  does  this  in  all  probabihty 
contaminate  the  swab  when  it  is  pushed  through  the  open  end,  but 
also  the  amount  is  often  so  considerable  as  to  run  down  the  inside 
of  the  tube  on  to  the  swab.  We  find  that  the  most  convenient  form 
of  swab  is  an  ordinary  diphtheria  swab,  with  the  last  quarter  of  an 
inch  bent  through  an  angle  of  about  45°.  This  can  be  carried  in  an 
ordinary  swab-tube  and,  being  small,  can  with  a  httle  practice  be 
easily  passed  under  the  arch  of  the  palate  at  either  side  of  the  uvula, 
rubbed  against  the  posterior  pharyngeal  wall,  and  quickly  withdrawn 
without  touching  any  other  structure  of  the  throat,  and  without  causing 
practically  any  distress  to  the  patient.  We  have  never  had  any  trouble 
at  all  with  a  carrier  at  the  second  and  subsequent  swabbings  by  this 
method,  and  we  have  come  to  the  conclusion,  that  in  our  hands  the 
numbers  of  different  organisms  grown  is  greater  with  West's  covered 
swab  than  with  this  simple  one.  The  discomfort  to  the  patient  is  also 
very  much  less.  There  is  a  still  further  difficulty  with  the  covered  swab 
method,  that  in  order  to  perform  it  with  comfort  it  would  be  necessary 
for  the  operator  to  possess  three  hands,  one  to  use  the  tongue  depressor, 
one  to  manipulate  the  glass  tube,  and  one  the  swab  wire.  It  is  an 
advantage  to  make  the  patient  draw  up  the  soft  palate  by  singing  "Ah" 
and  thus  exposing  the  posterior  pharyngeal  wall  to  a  greater  extent. 
The  slight  curve  at  the  end  of  the  ordinary  diphtheria  swab  enables  it 
to  shde  easily  high  up  the  posterior  pharyngeal  wall.  The  curve  on 
the  swab  has  an  additional  advantage,  in  that  the  parts  of  it  which 
are  most  likely  to  be  contaminated  are  the  point,  the  inner  part  of  the 
curve  by  the  soft  palate  on  withdrawal,  and  the  lower  surface  of  the 
straight  portion  by  the  tongue.  Now  it  is  very  easy  to  sow  the  swab 
on  to  the  plate,  only  using  the  outer  part  of  the  curved  portion, 
which  is  the  only  part  which  comes  in  contact  with  the  posterior 


x]  Eindemiology  135 

pharyngeal  wall,  and  is  also  the  part  which  is  least  likely  to  become 
contaminated. 

The  swab  having  been  taken,  it  must  be  sown  without  delay  on  to 
plates  of  one  of  the  special  media  on  which  the  meningococcus  will 
grow.  The  swab  is  sown  as  thickly  as  possible  on  to  a  spot  in  the 
plate  near  the  edge,  which  has  previously  been  marked  with  a  cross 
by  a  grease  pencil.  It  is  necessary,  when  swabs  are  taken  elsewhere 
than  in  the  laboratory,  to  carry  plates  as  well.  Some  form  of  sterilizable 
plate  holder  is  advisable.  A  simple  one  is  a  copper  cyUnder,  such  as 
documents  are  stored  in,  with  an  internal  copper  skeleton  frame,  which 
is  just  the  right  size  to  carry  the  plates,  and  can  be  partially  or  completely 
withdrawn  from  the  cyhnder.  Such  a  plate  carrier  can  easily  be 
sterihzed  at  frequent  intervals,  so  .  that  gross  contamination  of  the 
plates  is  avoided.  When  long  journeys  have  to  be  undertaken,  it  is 
advisable  to  adopt  some  method  of  keeping  the  plates  at  a  temperature 
in  the  region  of  37°  C.  This  can  be  managed  in  a  rough  way  by  carrying 
a  hot  water  bottle  in  a  bag,  in  which  the  plates  are  put,  but  a  better 
apparatus,  when  long  journeys  are  made  by  motor-car,  is  a  modification 
of  a  "Buckle"  basket,  such  as  is  supphed  by  the  Yorkshire  School  for 
the  BHnd.  The  sterilizable  plate  carrier  just  fits  into  a  felt-hned  tin, 
which  has  double  walls  and  bottom,  and  whose  intervening  space  can 
be  filled  with  water  at  37°  C.  A  close-fitting  felt-hned  lid  closes  the 
centre  of  the  cavity, 'which  is  thus  practically  surrounded  by  a  water 
jacket.  The  tin  fits  closely  into  a  wicker  basket,  which  has  a  thick 
felt-hned  padding  of  cotton  wool,  a  similar  loose  pad  covers  the  top  of 
the  tin  and  a  wicker  hd  closes  the  whole.  Such  an  apparatus  is  bulky, 
but  is  quite  convenient  for  carrying  in  a  motor  car.  It  has  been  carried 
for  eleven  hours  in  very  cold  weather,  with  a  drop  of  temperature  of 
less  than  1°.  It  is  best  to  leave  the  spreading  of  the  plates  until  they 
have  been  brought  back  to  the  laboratory;  they  can  then  be  con- 
veniently spread  by  a  freshly  made,  and  therefore  sterile,  capillary  tube 
bent  at  a  right-angle.  They  are  then  ready  for  incubation  at  37°  C. 
The  despatch  of  swabs  from  a  distance  by  messenger,  or  worse  still  by 
post,  is  practically  useless.  The  gram-negative  diplococcus  group  is 
extremely  dehcate,  and  will  not  survive  on  a  swab  for  any  length  of 
time.  The  figures  of  Bruns  and  Hohn  are  instructive,  for  though  it  is 
doubtful  that  they  sufficiently  diiierentiated  the  meningococcus  from 
other  gram-negative  cocci,  as  the  figures  they  give  are  extremely  high ; 
yet  a  progressive  diminution  in  positive  results  occurred,  according  to 
the  length  of  time  elapsing  between  the  taking  of  a  swab  and  its  sowing. 


136  Epidemiology  [cH. 

Of  swabs  sown  immediately  after  being  taken,  32  per  cent,  were  positive ; 
of  swabs  brougbt  by  special  messenger,  17  per  cent,  were  positive;  of 
swabs  sent  by  post  within  24  hours,  4-7  per  cent,  were  positive,  and  of 
swabs  sent  by  post  in  48  hours,  none  were  positive.  Their  figures  thus 
prove  that  there  is,  under  these  varying  circumstances,  a  very  marked 
diminution  of  vitahty  in  the  group  of  gram-negative  diplococci,  which 
includes  the  meningococcus.  It  is  therefore  always  necessary  that  all 
swabs  should  be  taken  in  the  laboratory,  or  that  the  necessary  apparatus 
should  be  carried  when  journeys  have  to  be  made. 

Carriers  have  already  been  discussed,  and  the  statement  has  been 
made  that  they  can  be  grouped  into  two  classes ;  transient  carriers 
and  prolonged  carriers.  A  further  sub-division  is  sometimes  made  of 
the  latter  class  into  prolonged  and  intermittent  carriers ;  but  inasmuch 
as  intermittent  carriers  are  merely  prolonged  carriers,  in  whom  periods 
occur  in  which  the  meningococcus  is  not  obtained  from  the  throat, 
there  is  really  Uttle  difference  between  them.  The  conditions  under 
which  the  meningococcus  is  carried  in  the  throat  are  in  fact  very  similar 
to  those  of  diphtheria  carriers,  where  also  the  organism's  stay  in  the 
throat  may  be  temporary  or  prolonged.  In  some  cases  the  length  of 
time  is  so  great  in  diphtheria  that  such  carriers  may  be  looked  upon  as 
permanent,  the  organism  existing  in  the  throat  for  years.  There  is  at 
present  no  evidence  that  the  meningococcus  can  be  carried  for  so  long 
a  time  as  this,  but  we  have  ourselves  known  a  carrier  to  be  positive  for 
six  months.  A  temporary  carrier  is  comparatively  easy  to  deal  with. 
The  organism  seldom  survives  for  as  long  as  a  fortnight  in  the  throat. 
In  a  number  of  cases  we  have  found  the  first  swab  positive,  while  the 
second  swab,  taken  some  ten  days  later,  and  all  subsequent  swabs 
proved  negative.  The  period  of  isolation  necessary  in  a  case  of  this 
kind  is  therefore  short.  Prolonged  carriers  are  very  much  more 
difficult  to  deal  with,  as  it  is  hardly  practicable,  even  in  the  case  of 
troops,  to  isolate  an  individual  for  as  long  as  six  months ;  the  problem 
is  a  similar  one  to  that  of  the  isolation  of  prolonged  diphtheria  carriers, 
which  is  at  present  still  without  a  satisfactory  solution.  The  mental 
depression  produced  by  prolonged  isolation  in  the  case  of  some  of  the 
carriers  among  the  troops  in  England  in  1915  became  very  serious. 
It  is  most  important  to  keep  such  carriers  occupied,  and  it  may 
perhaps  be  remarked  here  that  two  of  our  most  prolonged  carriers 
became  negative  shortly  after  being  given  a  definite  occupation; 
previous  to  this  they  had  found  time  hang  very  heavy  on  their  hands. 
It  is    just  conceivable  that  the  reaction  on  the  physical   condition. 


x]  Epidemiology  137 

produced  by  improvement  of  the  mental,  was  a  factor  in  the  destruction 
of  the  infection.  Another  matter  must  also  be  borne  in  mind;  it  does 
very  occasionally  occur  that  a  positive  contact  develops  the  disease, 
and  marked  mental  depression  may  be  a  factor  in  the  lowering  of 
resistance  which  enables  infection  to  take  place.  The  whole  problem 
of  the  treatment  of  these  prolonged  carriers  is  an  extremely  difficult 
one,  but  a  reasonable  occupation  should  always  be  provided  for  them. 
On  all  grounds  it  is  important  that  they  should  be  in  the  open  air  as 
much  as  possible. 

Local  treatment  of  the  throat  does  not  appear  to  be  very  satisfactory ; 
it  is  doubtful  whether  it  has  much  effect.  Gargles  and  sprays  are  of 
very  httle  use,  as  they  hardly  touch  any  structures  further  back  than 
the  soft  palate,  and  uvula.  The  posterior  wall  of  the  pharynx  especially 
in  its  upper  regions  is  entirely  untouched  by  them.  The  same  dis- 
advantages hold  with  sprays  or  paints  applied  through  the  nares,  which 
seldom  reach  beyond  the  inferior  turbinate  bone.  The  use  of  a  mild 
antiseptic  as  a  nasal  douche  is  a  more  reasonable  proceeding,  as  the 
antiseptic  can  be  introduced  in  quantity  into  the  upper  regions  of  the 
nose  and  made  to  return  through  the  mouth;  the  antiseptic  is  thus 
brought  into  contact  with  the  posterior  regions  of  the  nose  and  the 
posterior  pharyngeal  wall,  even  in  its  upper  portions.  We  have  found 
that  a  solution  of  potassium  permanganate  in  1-5  per  cent,  sodium 
sulphate  of  the  strength  of  1  in  1000,  diluted  with  an  equal  quantity 
of  warm  water,  wiU  cause  meningococci  to  disappear  from  the  posterior 
pharyngeal  secretion  when  used  three  or  four  times  a  day  in  a  nasal 
irrigator.  This  disappearance  is,  however,  only  transient,  the  cocci  in 
most  cases  reappearing  within  48  hours.  We  never  examine  the  throat 
of  a  carrier  until  48  hours  have  elapsed  since  the  last  douching. 
It  is  very  questionable  whether  the  permanent  disappearance  of  the 
meningococcus  has  ever  been  hastened  by  these  means.  We  have 
found  that  temporary  carriers  have  lost  the  meningococcus  in  quite  a 
short  time,  when  no  treatment  at  all  had  been  pursued ;  again  prolonged 
carriers,  in  whom  local  treatment  has  been  given  up,  have  suddenly 
been  found  no  longer  to  carry  the  meningococcus  in  the  throat. 
The  use  of  stronger  antiseptics  is  of  doubtful  benefit,  for  there  is 
always  the  danger  of  damage  to  the  dehcate  mucous  membrane  of  the 
posterior  regions  of  the  nose.  The  use  of  a  mild  antiseptic  in  a  nasal 
douche  is  therefore  the  most  reasonable  treatment  on  our  present 
knowledge,  but  it  cannot  be  maintained  that  any  very  definite  value 
has  been  proved  for  such  treatment. 


138  Epidemiology  [CH.  x 

The  conclusions  of  this  chapter  can  be  shortly  stated  as  follows. 
The  cause  of  epidemic  cerebro-spinal  meningitis,  the  meningococcus  of 
Weichselbaum,  is  spread  by  direct  contagion  from  person  to  person, 
the  organism  being  carried  in  the  nose  and  throat.  The  presence  of 
the  organism  in  the  throat  is  not  indicated  by  any  obvious  sign;  the 
throats  of  carriers,  whether  they  are  convalescent  patients,  or  have 
never  sufEered  from  the  disease,  are  chnically  normal.  Carriers  can  be 
divided  into  two  classes,  temporary  and  prolonged,  the  latter  being 
the  most  important  from  the  preventive  point  of  view,  and  also  by  far 
the  most  difficult  to  deal  with.  Carriers  should  be  isolated  as  far  as 
sleeping  and  eating  are  concerned,  and  should,  if  possible,  be  given 
an  occupation  in  the  open  air.  The  local  treatment  of  the  throat  is 
not  very  satisfactory,  a  mild  antiseptic  in  a  nasal  douche  being  the 
best  method.  The  disease  is  a  disease  of  winter  and  spring,  occurring 
mainly  in  temperate  climates;  it  appears  to  be  associated  with  over- 
crowding and  bad  ventilation,  and  also  is  most  hable  to  break  out  in 
any  given  community  when  rapid  changes  take  place  in  the  population 
forming  it.  It  is  present  in  most  civihzed  countries  in  an  endemic 
form,  as  posterior  basic  meningitis  of  infants.  Epidemics  affect  mainly 
the  children  in  a  civihan  population,  but  may  also  attack  troops ;  in 
the  latter  case,  the  type  of  disease  is  a  very  severe  one. 


CHAPTER   XI 

THE   BACTERIOLOGY   OF   THE   MENINGOCOCCUS   AND   OTHER 
GRAM-NEGATIVE   DIPLOCOCCI 

Gram-negative  diplococci  numerous  especially  in  naso-pharynx. 
The  meningococcus  probably  not  a  single  species  but  a  group. 
Characters  of  gram-negative  diplococci,  morphology,  staining  reactions, 
behaviour  to  Gramas  stain,  intracellular  position  characteristic  of 
group,  vitality,  characters  of  colonies.  Differentiation  of  the  meningo- 
coccus from  the  gonococcus,  from  the  rest  of  the  group,  mainly  dependent 
on  sugar  reactions,  our  oivn  classification,  other  classifications. 
Characteristics  of  meni^igococcus,  morphology  and  staining  power, 
culture,  corn  starch  medium  of  Tedder,  characters  of  colony,  large 
and  small  colonies,  inhibition  of  growth,  temperatures  of  growth,  effect 
of  sunlight,  of  desiccation,  of  disinfectants,  pathogenicity  to  animals, 
toxins.  Characters  of  M.  Pharyngis  Siccus,  of  M.  Flavus  I,  of  M. 
Flavus  II,  of  M.  Flavus  III,  of  M.  Catarrhalis.  Fermentation  re- 
actions, difficulties  of  preparation  of  media,  reactions  lengthy  and  often 
slightly  marked,  serum  broth  medium,  starch  broth  medium,  las' 
medium,  fermentation  reactions  of  group,  of  meningococcus,  of 
M.  Catarrhalis.  Agglutination  reactions,  earlier  work,  investigations 
of  Elser  and  Huntoon,  absorption  reaction,  their  method,  Gordon^s 
grouping  of  strains,  pseudo-meningococcus,  para-meningococcus 
of  Dofter.  Opsonic  tests,  complement  fixation  test,  precipitin  test, 
method  of  investigating  plate  cultures  from  posterior  pharynx. 

The  meningococcus  belongs  to  the  gram-negative  diplococci,  a  group 
of  organisms  which  are  numerous  and  have  not  yet  been  satisfactorily 
differentiated.  The  other  most  well-kno^n  organism  in  this  group  is  the 
gonococcus,  which  has  been  studied  to  a  considerable  extent,  because  it 
is  also  a  pathogenic  organism.  There  are,  however,  a  number  of  other 
members  belonging  to  the  group  which  have  been  studied  comparatively 
httle,  because  in  most  cases  they  have  no  pathogenic  properties.  They 
commonly  inhabit  the  posterior  regions  of  the  nose  and  pharynx,  and  have 
seldom  been  observed  elsewhere.  It  has  already  been  stated  that,  on 
present  evidence,  the  probabihties  are  that  the  meningococcus  is  almost 
exclusively  carried  in  the  posterior  pharynx,  its  differentiation  from  other 
members  of  the  group  is  therefore  a  matter  of  extreme  importance. 


140  Bacteriology  [ch. 

There  is  one  other  member  of  the  group  which  is  pathogenic,  namely, 
micrococcus  catarrhahs;  this  organism  gives  rise  to  naso-pharyngeal 
catarrh,  and  is  often  extremely  difficult  to  differentiate  from  the  meningo- 
coccus. It  has  previously  been  stated  that  we  are  inchned  to  the  view 
that  a  confusion  between  micrococcus  catarrhahs  and  the  meningococcus 
is  the  reason  for  the  description  of  a  catarrhal  stage  in  meningococcal 
infections.  The  differentiation  of  the  meningococcus  is  complicated  by 
the  fact  that  it  is  doubtful  whether  it  is  really  one  specific  organism,  it 
is  more  likely  that  a  group  of  closely  alhed  organisms  exists,  any  one 
of  which  may  be  the  cause  of  epidemic  meningitis.  The  evidence  for 
this  will  be  discussed  later;  it  has  already  been  touched  upon  iru 
Chapter  VIII  when  discussing  the  reactions  of  the  body  to  infection. 
This  multiplicity  of  strains  is  possibly  the  reason  why  all  work  on  the 
biological  properties  of  the  organism  has  been  so  confficting. 

The  group  of  organisms  which  have  to  be  discussed  in  this  chapter 
have  the  following  common  characteristics.  They  are  all  diplococci, 
that  is  to  say  they  commonly  appear  in  pairs.  Occasionally  both  in  body 
fluids  and  culture  they  also  appear  in  tetrads,  as  is  shewn  in  Plate  XI, 
fig.  2.  The  two  members  of  a  pair  are  usually  flattened  on  that  side 
on  which  they  are  close  to  one  another,  so  that  they  look  as  though 
they  had  been  pressed  together,  the  long  axis  of  the  individual  lying 
at  right  angles  to  the  long  axis  of  the  pair.  They  may  be  flattened 
to  such  an  extent  as  to  look  hke  a  single  coccus  with  a  division  down 
the  middle.  The  size  of  the  individual  coccus  varies  very  greatly, 
some  members  of  the  group  tend  to  vary  in  this  respect  considerably 
more  than  others,  but  no  difierentiation  can  be  made  on  these  hues, 
as  all  the  members  of  the  group  will  at  some  time  or  other  be  found  to 
shew  variations.  The  mean  size  of  the  organism  is  also  useless  for 
differentiation,  though  some  tend  on  the  whole  to  be  larger  than  others. 
Identification  in  any  particular  instance  by  the  size  of  the  organism  is 
valueless.  The  variation  in  .the  size  of  individuals  in  any  particular 
culture  is  also  more  marked  in  the  case  of  certain  organisms,  the 
meningococcus  being  especially  prominent  in  this  respect  both  in 
culture  and  body  fluids.  Occasionally,  however,  we  have  found  that 
some  other  organism  undergoing  daily  sub-culture,  which  has  remained 
fairly  constant  in  shape  and  size,  suddenly  shews  irregularities  as  great 
as  those  of  the  meningococcus. 

Irregularities  in  staining  reaction  are  also  common  throughout  the 
group.  It  is  frequently  found  in  culture  that,  on  making  a  film,  numbers 
of  the  organisms  stain  very  badly,  this  does  not  seem  to  depend  on  the 


xi]  Bacteriology  141 

age  of  the  culture,  for  it  is  often  observed  in  cultures  under  24  hours 
old.  Certain  organisms,  the  meningococcus  among  them,  shew  this 
pecuharity  more  commonly  than  others,  but  any  member  of  the  group 
may  at  times  shew  it  to  a  very  marked  degree.  It  has  been  stated  that 
this  loss  of  staining  power,  when  extensive,  means  that  the  greater  number 
of  the  organisms  are  dead.  But  the  view  that  an  organism  which  stains 
badly  has  lost  its  vitahty  is  a  pure  assumption,  and  in  the  group  imder 
consideration  is  not  borne  out  by  the  facts.  When  the  vitahty  of  the 
meningococcus  and  alHed  organisms  comes  to  be  disciissed,  it  vnVi.  be 
seen  that  the  best  method  for  retaining  the  vitahty  in  any  particular 
strain  is  to  sow  it  in  a  starch  stab.  It  is  extremely  common  to  find, 
when  sub-culturing  from  such  a  stab  a  fortnight  or  more  old,  that 
though  the  sub-culture  grows  very  strongly,  the  organisms,  which 
compose  it,  all  stain  extremely  badly.  There  is  no  question  that  the 
staining  properties  of  an  organism  must  depend  upon  the  composition 
of  its  protoplasm,  but  there  is  no  reason  why  the  absence  of  the 
staining  constituent  should  imply  that  the  vitahty  of  the  protoplasm  is 
destroyed;  certain  organisms  always  stain  badly,  such  as  the  members 
of  the  coh  group,  and  some,  though  in  the  summit  of  their  vigour,  for 
example  the  tubercle  baciUus,  do  not  stain  at  all  by  the  routine  methods 
ordinarily  used. 

The  group  belongs  to  the  staphylococci,  not  the  streptococci,  as  can 
be  easily  seen  when  grown  in  fluid  culture.  They  are  never  found  in  true 
chains,  though  short  lengths  of  false  chains  may  occasionally  be  seen 
in  cultures  on  sohd  media.  These  false  chains  are  formed  by  pairs  of 
cocci  lying  alongside  one  another,  so  that  the  long  axis  of  the  pair  is 
at  right  angles  to  the  axis  of  the  chain.  This  false  chain  formation 
is  only  occasionally  met  with,  but  occurs  in  all  members  of  the  group. 

The  characteristic  by  which  the  group  is  separated  from  other 
staphylococci,  and  also  from  certain  members  of  the  streptococcal  group, 
which  frequently  occur  in  pairs,  such  as  the  pneumococcus,  is  their 
inabihty  to  retain  the  stain  by  Gram's  method  of  staining;  they  are 
therefore  known  as  the  gram-negative  diplococci.  The  method  of 
employing  Gram's  stain  that  we  have  used,  is  to  stain  for  five  minutes 
with  carbol  gentian  violet,  blot,  treat  with  Gram's  iodine  for  one 
minute,  blot,  and  then  decolourize  for  three  minutes  with  absolute 
alcohol.  After  again  blotting,  the  film  is  counter-stained  with  Bismark 
brown,  and  then  examined  in  water  by  inverting  the  covershp  and 
blotting.  Certain  other  organisms,  which  occur  fairly  commonly  in  the 
air  -and  can  therefore  contaminate  plates  and  cultures,  have  also  the 


142  Bacteriology  [CH. 

form  of  gram-negative  diplococci.  These  organisms  are,  however,  very 
large,  grow  extremely  abundantly  on  any  medium  at  any  temperature, 
and  belong  rather  to  the  group  of  sarcinae.  They  therefore  cause  Uttle 
difficulty,  and  can  be  readily  eliminated.  As  in  our  experience  they 
never  occur  in  the  posterior  pharynx,  but  are  always  introduced  as 
a  contamination,  their  properties  need  not  be  further  discussed.  It  is, 
however,  important  to  recognize  their  existence;  one  of  our  earUest 
encounters  with  them  was  in  a  sample  of  serum  that  we  were  using  to 
make  media,  and  at  first  this  contamination  caused  us  considerable 
trouble  and  uncertainty.  The  question  of  the  gram-negative  character 
of  the  group,  and  of  the  meningococcus  in  particular,  has  caused  much 
discussion.  In  Weichselbaum's  original  description  the  meningococcus 
was  described  as  being  always  gram-negative,  but  the  work  of  Jaeger 
and  Heubner  caused  confusion  to  arise  in  this  matter,  as  they  described 
various  forms  of  organisms,  both  gram-positive  and  gram-negative,  as 
the  cause  of  epidemic  meningitis.  More  modern  work  has  however  shewn 
that  the  organism  is  gram-negative,  and  Gordon  and  others  claim  that 
the  meningococcus  is  invariably  so.  This  is  not  strictly  correct,  for  we 
have  found  that,  in  sub-culture  under  certain  circumstances,  the  meningo- 
coccus undoubtedly  becomes  to  some  extent  gram-positive.  The  whole 
culture  never  becomes  gram-positive,  but  only  a  certain  minority  of  the 
individuals  forming  it.  We  have  exhausted  every  means  that  occurred 
to  us  to  prove  that  this  was  a  true  change  in  the  meningococcus  and  not 
due  to  the  introduction  of  some  contamination,  but  whatever  methods 
were  used,  either  of  dilution,  sowing  from  individual  colonies,  or  plating, 
we  have  always  obtained  pure  cultures  of  meningococcus  only.  We  are, 
however,  in  entire  agreement  that  the  meningococcus,  when  first  obtained 
from  cerebro-spinal  fluid  or  the  posterior  pharynx,  is  invariably  com- 
pletely gram-negative ;  it  is  only  under  certain  conditions  of  sub-culture 
that  the  gram-positive  forms  appear.  One  of  the  most  certain  methods 
to  produce  them  is  to  expose  the  culture  to  sunhght.  These  properties 
also  apply  to  other  members  of  the  group,  all  when  first  obtained  are 
completely  gram-negative.  Some,  however,  have  the  power  of  pro- 
ducing in  sub-culture  gram-positive  forms  with  greater  ease  than  the 
meningococcus,  others  again  hardly  ever  produce  them.  The  character- 
istics of  the  group  with  respect  to  Gram's  stain  are  therefore  these; 
when  first  obtained  all  are  entirely  gram-negative,  but  under  certain 
conditions  of  sub-culture,  any  one  may  shew  gram  staining  to  a  greater 
or  less  degree. 

Another  characteristic  is  common  to  the  whole  group ;    when  found 


xi]  Bacteriology  143 

in  any  exudate  from  the  body,  the  organisms  are  almost  entirely  intra- 
cellular, lying  within  the  bodies  of  polymorphonuclear  leucocytes.  This 
is  in  striking  contrast  to  the  usual  distribution  of  cocci  in  such  fluids. 
The  organisms  he  in  pairs  in  the  cytoplasm,  occasionally  in  tetrads 
(Plate  XI,  fig.  2),  and  shew  considerable  differences  in  size  and  staining 
power.  It  is  owing  to  this  characteristic  that  the  meningococcus  is 
often  called  the  micrococcus  intracellularis  meningitidis. 

The  vitality  of  the  organisms  composing  the  group  is  very  similar, 
Aough  a  distinct  grading  in  power  of  growth  exists  from  one  end  of 
the  scale  to  the  other.  The  meningococcus  and  gonococcus  are  the 
most  difficult  to  grow.  None  of  the  members  of  the  group  grow  over- 
readily  on  ordinary  media;  neither  can  any  be  kept  ahve  indefinitely 
without  the  use  of  special  media.  The  best  medium  for  the  whole 
group  is  undoubtedly  blood  agar,  that  is  to  say,  ordinary  agar  with 
a  few  drops  of  fresh  blood  added  just  before  it  is  allowed  to  set.  Other 
media  containing  other  body  fluids,  such  as  serum,  ascitic  fluid,  or 
hydrocele  fluid,  are  also  efficient.  AU  methods,  which  are  satisfactory 
for  the  meningococcus,  are  found  to  be  satisfactory  for  the  whole  group. 

The  appearance  of  the  colony  under  the  low  power  of  the  microscope 
is  characteristic  throughout  the  group  and  is  easily  recognizable  if  a 
transparent  medium  is  used,  such  as  nutrose  serum  agar*.  The  various 
members  of  the  group  cannot  be  differentiated  with  certainty  from  one 
another  by  the  appearances  of  the  colony,  as  these  are  frequently  much 
ahke.  The  low  power  of  the  microscope  is  however  extremely  valuable 
for  picking  out  gram-negative  diplococci  on  such  a  medium.  The 
colonies  are  large,  being  much  larger  than  those  of  any  of  the  strepto- 
cocci, but  are  of  the  same  size  as  colonies  of  the  staphylococci.  They 
differ  from  the  latter  however  in  being  comparatively  hght  in  colour 
and  clear.  Their  colour  varies  from  a  pale  yellow  to  a  deep  orange 
brown,  according  to  the  amount  of  pigment  in  them.  It  is  on  the  whole 
true  that  the  palest  are  the  meningococcus  and  micrococcus  catarrhalis, 
while  the  darkest  are  members  of  the  flavus  group.  A  particular  strain 
of  the  latter  may  however  lose  a  considerable  part  of  its  pigment  in 
sub-culture,  or  it  may  not  develop  that  pigment  in  the  primary  colony 
when  first  obtained,  it  is  therefore  unsafe  to  rely  on  this  property  for 
differentiation.  The  colonies  are  always  smooth  with  a  regular  circular 
edge  when  only  24  hours  old,  and  perfectly  clear  with  no  granulation 
or  striation  visible  in  them.  Forty-eight  hour  cultures  may  exhibit 
a  scattered  punctiform  pigmentation  in  the  centre  of  the  colony,  the 
*  See  Appendix  II. 


144  Bacteriology  [ch. 

outer  zone  still  remaining  clear,  but  this  pigmentation  is  quite  unlike 
the  granular  appearance  seen  in  colonies  of  streptococci.  In  a  24  hours' 
growth  the  yellow  colour  is  most  intense  over  the  inner  part  of  the 
colony,  the  outer  zone  being  paler  and  still  more  transparent.  There 
are  few  other  organisms  with  colonies  of  this  description  occurring  in 
the  naso-pharynx.  Occasionally  a  cohform  organism  is  met  with,  which 
is' very  similar,  and  some  of  the  streptococci  have  similar  clear  colonies, 
but  in  the  latter  case  these  colonies  are  always  very  much  smaller  than 
those  of  the  gram-negative  diplococci.  The  staphylococci  are  easily 
separated,  as  their  colonies  are  almost  black.  Hofimann's  baciUus, 
which  is  fairly  frequently  met  with,  is  also  dark  and  usually  granular, 
though  its  colonies  are  often  the  same  size  as  those  of  the  gram-negative 
group  of  cocci. 

The  other  biological  characters  of  the  group  ^vill  be  discussed  later, 
when  dealing  with  agglutination  reactions. 

The  differentiation  of  the  meningococcus  from  the  other  members 
of  the  group  is  still  a  matter  of  difficulty,  but  is  of  the  utmost  importance 
when  deahng  with  the  examination  of  the  naso-pharynx.  One  organism 
can,  however,  be  ehminated  for  practical  purposes  from  consideration, 
namely,  the  gonococcus.  This  organism  is  in  the  majority  of  instances 
an  inhabitant  of  the  urogenital  tract  only,  and  an  infection  can  only 
occur  by  direct  contact  from  one  individual  to  another.  It  is  doubtful 
if  it  has  ever  been  obtained  from  the  posterior  pharynx.  It  is  also 
doubtful  whether  it  is  ever  the  cause  of  meningitis,  though  instances 
of  this  have  been  described.  On  these  grounds  it  is  therefore  un- 
necessary to  consider  the  methods  of  differentiation  of  the  meningococcus 
and  gonococcus  in  this  book ;  the  matter  is  not  an  easy  one,  and  depends 
partly  on  the  power  of  the  meningococcus  to  ferment  maltose,  a  power 
which  the  gonococcus  does  not  possess.  The  differentiation  by  agglu- 
tinating reactions  is  difficult,  as  also  is  the  differentiation  by  complement 
fixation,  for  cross  fixation  may  take  place  to  some  considerable  degree. 
On  our  present  knowledge  it  is  reasonable  to  leave  the  gonococcus  out 
of  consideration,  when  considering  infections  of  the  cerebro-spinal 
system  or  of  the  pharynx. 

The  characteristics  of  the  meningococcus  will  now  be  considered  in 
detail,  and  then  the  dift'erences  that  each  of  the  other  members  of  the 
group  possess.  It  will  however  be  convenient  first  to  state  the  classi- 
fication which  we  intend  to  adopt.  Our  classification  in  the  main 
depends  upon  the  power  of  fermentation  of  various  carbo-hydrates,  and 
it  is  therefore  as  well  to  give  their  characteristics  in  this  respect  in  the 


xi]  Bacteriology  145 

form  of  a  table.     The  details  of  these  reactions  and  the  difficulties 
attending  them  will  be  discussed  later. 


Glucose 

Maltose 

Laevulose 

Saccharose 

M.  pharyngis  siccus 

M.  flavus I 

M.  flavus  II 

M.  flavus  III 

+  1 

+  2 
+  4 
+  4 

+  1 

+  2 
+  4 
+  4 

+  1 
+  2 

+  4 
+  4 

+  1 
+  2 
+  4 

Meningococcus           1 
Para-meningococcusJ 
Gonococcus  ... 
M.  catarrhalis 

+  4 
+  4 

+  4 

- 

- 

The  figures  shew  the  first  day  on  which  a  marked  reaction  is  obtained. 

It  will  be  seen  that  seven  difierent  organisms  are  given  'W'ith  different 
fermentation  reactions,  the  meningococcus  and  para-meningococcus  being 
identical  in  this  respect  and  therefore  falling  into  one  group.  The  chief, 
characteristics  of  these  organisms,  rehed  on  for  their  differentiation, 
may  be  stated  here,  so  as  to  facihtate  their  subsequent  more  detailed 
description. 

Micrococcus  Pharyngis  Siccus. 

White  in  colour,  grows  very  readily  and  ferments  glucose,  maltose, 
saccharose  and  laevulose  in  a  few  hours.  Grows  strongly  at  23°  C. 
When  growTi  at  37°  C.  the  culture,  even  in  24:  houis,  gets  a  skin  over  it, 
which  is  adherent  to  the  medium. 

M.  Flavus  I. 

Orange  yellow  in  colour,  this  however  varies  in  depth  mth  different 
strains.  Ferments  glucose,  maltose,  saccharose  and  laevulose,  but  often 
takes  two  days  to  shew  this  reaction  strongly,  especially  in  the  case  of 
saccharose  and  laevulose.  Grows  strongly  at  23°  C.  When  grown  at 
37°  C.  the  colonies  tend  to  shde  about  on  the  medium,  and  the  growth 
is  rather  drier  than  that  of  the  others  in  the  group. 

M.  Flavus  II. 

Also  orange  yellow  in  colour.  It  is  a  much  more  delicate  organism, 
growing  slower  and  fermenting  glucose,  maltose,  saccharose  and  laevu- 
lose, but  much  more  slowly  and  less  completely  than  flavus  I.  It  often 
takes  three  to  four  days  to  shew  any  reaction ;  the  reaction  may  appear 
first  in  saccharose.  At  23°  C.  it  grows  extremely  feebly,  seldom  being 
obvious  in  less  than  48  hours.  When  grown  at  37°  C.  the  colonies  tend 
to  coalesce  into  a  rather  sticky  mass,  often  coming  away  in  strings  when 
touched  by  a  needle. 

F.  &G.  -10 


146  Bacteriology  [CH. 

M.  Flavus  III. 

Canary  yellow  in  colour,  which  in  pure  culture  is  often  quite 
distinct  from  that  of  flavus  I  and  II.  It  is  a  more  delicate  organism 
than  flavus  I,  but  not  so  delicate  as  flavus  II.  It  ferments  glucose, 
maltose  and  laevulose,  but  not  saccharose,  taking  three  to  four  days 
in  producing  a  strong  reaction.  With  regard  to  growth  at  23°  C.  two 
varieties  are  met  with,  one  III  A,  which  grows  fairly  strongly  at  this 
temperature,  nearly  as  well  as  flavus  I,  the  other  III  B,  which  refuses 
to  grow  at  all  at  23°  C,  but  grows  slightly  between  24°  C.  and  25°  C. 
When  grown  at  37°  C,  the  consistency  of  the  colony  is  like  wet  paint, 
thus  closely  resembhng  the  meningococcus. 

The  Meningococcus  and  Para-meningococcus. 

These  two  organisms  are  culturally  practically  identical  and  will  be 
described  together.  The  colour  is  white  or  very  faintly  yellow.  They 
ferment  glucose  and  maltose  but  not  laevulose  or  saccharose.  The 
reaction  usually  takes  three  or  four  days  to  be  marked.  At  23°  0.  they 
usually  do  not  grow,  occasionally  however  a  sHght  growth  has  been 
obtained,  and  between  24°  C.  and  25°  C.  growth  may  at  times  be  quite 
considerable.  When  grown  at  37°  C.  the  consistency  of  the  colonies  is 
like  wet  paint. 

The  Gonococcus. 

The  growth  is  very  similar  to  that  of  the  meningococcus,  it  ferments 
glucose  but  not  maltose,  laevulose  or  saccharose.  As  it  is  of  httle 
importance  for  the  present  discussion,  its  properties  will  not  be  further 
considered. 

M.  Catarrhalis. 

The  colour  is  white  and  the  growth  is  strong,  it  does  not  ferment 
any  sugar,  either  glucose,  maltose,  laevulose  or  saccharose.  It  grows 
very  poorly  in  the  cold  at  23°  C.  in  some  cases  practically  entirely  faihng 
to  grow.  The  consistence  of  the  culture  is  hke  that  of  the  meningo- 
coccus. 

It  is  clear  from  the  above  descriptions  that  the  sugar  fermentation 
tests  are  very  slow,  especially  in  the  case  of  the  groups  flavus  II  and 
III  and  the  meningococcus.  In  these,  reactions  occur  at  about  the 
same  rate  and  are  only  certain  in  three  to  four  days.  It  is  therefore 
always  necessary  to  keep  sugar  tubes  for  at  least  a  week.  The  test  of 
growth  at  23°  C.  is  of  partial  value,  for  M.  pharyngis  siccus,  M.  flavus  I 


xi]  Bacteriology  147 

and  M.  flavus  III  A  all  grow  strongly  at  this  temperature;  the  others, 
M.  flavus  II,  M.  flavus  III  B,  the  meningococcus  and  M.  catarrhalis 
cannot  be  differentiated  by  this  test,  as  none  of  them  grow  strongly, 
but  any  of  them  may  shew  shght  growth.  The  method  of  testing  the 
power  to  grow  at  23°  C.  is  the  following.  A  slope  is  sown  with  a  good 
needle-full  of  culture  as  uniformly  as  possible  over  the  surface.  It  is 
even  more  important  to  sow  fairly  thickly  for  this  test  than  when 
maldng  an  ordinary  sub-culture,  for  if  this  is  not  done  an  organism 
frequently  fails  to  grow  which  will  grow  quite  well  if  thickly  sown. 
The  culture  is  kept  in  a  cold  incubator  at  23°  C.  for  two  or  three  days ; 
if  at  the  end  of  this  period  no  obvious  growth  has  been  obtained,  the 
tube  is  transferred  to  the  37°  C.  incubator.  A  copious  growth  should 
be  obtained  at  this  temperature  in  24  hours.  If  no  growth  is  obtained, 
the  test  should  be  repeated,  as  the  failure  to  grow  at  23°  C.  may  be  due 
to  the  early  death  of  the  sub-culture.  We  have  tested  a  large  number 
of  meningococci  in  this  manner,  and  have  always  found  that,  if  they 
are  properly  sown,  we  can  obtain  a  good  growth  at  37°  C.  when  trans- 
ferred from  the  cold  incubator.  The  above  classification  is  very  similar 
to  that  of  Elser  and  Huntoon,  with  the  difference  that  the  chromogenic 
or  flavus  group  is  not  subdivided  in  exactly  the  same  manner.  Our 
groups  flavus  I  and  II  would  both  fall  within  their  chromogenic  group  I, 
as  they  both  ferment  glucose,  maltose,  laevulose  and  saccharose.  Their 
chromogenic  group  II  corresponds  with  our  flavus  III  group.  Their 
chromogenic  group  III  only  ferments  glucose  and  maltose  and  does  not 
affect  laevulose  and  saccharose.  We  have  performed  experiments  with 
laevulose,  and  have  found  that  all  strains  of  M.  flavus  III,  which  we 
have  obtained,  will  ferment  this  sugar;  it  is  therefore  possible  that  we 
have  not  met  with  Elser  and  Huntoon's  chromogenic  group  III.  Other 
observers  give  still  other  carbohydrate  reactions  for  the  purpose  of 
differentiation  of  the  gram-negative  diplococci.  These  will  be  discussed 
later  in  deahng  in  detail  with  the  fermentation  powers  of  the  various 
groups.  The  earHest  classifications  were  attempted  by  von  Lingelsheim 
and  others  by  means  of  agglutination  reactions,  but  these  reactions 
are  extremely  indefinite  throughout  the  group  and  are  unreliable  for 
classification  purposes.  The  test  of  the  power  of  growth  at  23°  C.  is 
claimed  by  Gordon  to  be  of  very  great  value,  all  members  of  the 
group  growing  at  this  temperature  except  the  meningococcus  and 
para-meningococcus.  We  are,  however,  unable  to  agree  that  all  the 
other  members  of  the  group  grow  at  this  temperature,  but  have  found 
a   considerable   number   of   organisms   in   the   flavus    and    catarrhalis 


148  Bactcriologji  [CH. 

groups,  which  either  do  not  grow  at  all,  or  grow  extremely  badly.  The 
earliest  observers  also  attempted  to  rely  on  morphological  characteristics 
for  difierentiation.  From  what  has  already  been  said,  such  methods 
are  clearly  practically  useless. 

The  characteristics  of  the  meniagococcus  will  now  be  described. 

The  Meningococcus. 

It6  morphological  characters  have  already  been  described  when 
dealing  with  the  whole  group  of  gram-negative  diplococci.  There  are 
a  few  peculiarities  which,  though  shght  and  not  sufficient  for  identifica- 
tion of  the  organism,  may  be  mentioned  here.  In  size  and  staining 
power  the  meningococcus  very  frequently  shews  great  variations,  when 
cultured  on  sofid  media.  The  pairs  may  be  small  and  regular,  and  then 
possess  fairly  uniform  staining  power;  or  they  may  be  variable,  the 
largest  being  considerably  bigger  than  the  cocci  of  a  staphylococcus 
culture ;  their  staining  reaction  also  is  then  very  variable.  Sometimes 
in  culture  by  far  the  larger  number  of  organisms  hardly  stain  at  aU, 
though  scattered  throughout  the  field  are  pairs  which  take  the  stain 
quite  deeply.  Cultures  are  also  met  with,  in  which  no  weU-stained 
organisms  are  to  be  found.  We  have  found  such  cultures  most 
frequently  when  first  sowing  from  a  starch  stab  some  ten  days  to  a 
fortnight  old.  As  already  mentioned,  we  do  not  consider  that  this  lack 
of  staining  has  much  relation  to  the  ^ataUty  of  the  cidture.  A  granular 
staining  is  also  not  uncommon,  it  occurs  usually  in  cultures  which  are 
beginning  to  shew  badly  staining  forms.  With  methylene  blue  and 
other  stains  certain  organisms  are  found  to  shew  darkly  staining  granules 
in  an  otherwise  very  feebly  staining  cell  body.  They  are  probably 
identical  with  certain  metachromatic  granules,  which  have  been  de- 
scribed by  Councilman,  MaUory  and  Wright.  In  flmd  media  the 
meningococcus  shews  that  it  belongs  to  the  staphylococcus  gi'oup,  no 
true  chains  being  found.  The  meniagococcus  when  first  obtained  is 
always  completely  gram-negative;  it  usually  continues  to  be  so  in 
sub-culture,  but  under  certain  circumstances  it  may  shew  a  number 
of  gram-positive  forms.  These  are  usually  found  in  old  cultures  of 
48  horns'  growth  or  more ;  they  can,  however,  often  be  quickly  obtained 
by  exposing  the  culture  to  siinhght.  When  examining  cerebro-spinal 
fluids  either  freshly  obtained  or  incubated,  pairs  of  cocci  are  often  seen 
which  appear  to  shew  capsiiles,  for  a  clear  zone  appears  round  the 
bodies  of  the  cocci,  and  contrasts  ■with  the  more  deeply  stained  pro- 
toplasm of  the  leucocytes  or  their  degenerated  debris  (Plate  XI,  fig.  2). 


xi]  Bacteriology  149 

A  similar  appearance  can  also  be  seen  in  sections  of  the  brain  and 
meninges  (Plate  XI,  fig.  1).  This  zone  is  not  usually  considered  to  form 
a  true  capsule,  as  it  does  not  stain  and  can  never  be  found  in  culture. 
It  is,  however,  possible  that  a  form  of  capsule  does  exist,  but  only  when 
the  organisms  are  within  tissues. 

The  culture  of  the  meningococcus  is  a  matter  of  some  difficulty,  and 
requires  special  media  for  its  successful  performance.  It  is  true  that 
the  organism  will  grow  to  some  extent  on  ordinary  agar,  but  strains 
cannot  be  kept  ahve  on  this  medium,  as  the  second  or  third  sub-culture 
fails.  The  organism  was  first  cultivated  by  Weichselbaum  on  agar  with 
2  per  cent,  gelatine  added  to  it,  he  found  however  that  it  was  necessary 
to  sub-culture  at  least  every  two  days.  Since  then  other  media  have 
been  devised  which  are  suitable  for  the  growth  of  the  organism,  all 
of  which  have  this  in  common,  that  the  addition  of  some  body  fluid 
is  necessary.  Whatever  fluid  is  used,  it  is  necessary  to  collect  it  in 
a  sterile  manner,  and  add  it  to  agar  when  sterihzation  is  complete  and 
the  agar  has  cooled  to  about  40°.  The  tube  is  then  well  mixed  and 
allowed  to  set  in  a  slope.  The  medium  on  which  the  freest  growth  is 
obtained  is  blood  agar,  that  is  to  say,  agar  to  which  about  three  drops 
of  fresh  sterile  blood  have  been  added  in  the  manner  just  described. 
The  rabbit  is  a  convenient  animal  from  which  to  obtain  blood  for  this 
purpose.  We  have  frequently  obtained  positive  cultures  from  cerebro- 
spinal fluid  on  blood  agar,  when  other  forms  of  medium  have  entirely 
failed  to  grow  the  organism.  It  is  therefore  always  advisable  to  use 
this  medium  when  deahng  with  a  new  case,  or  when  a  stage  of  disease 
is  reached  at  which  the  organism  cannot  be  obtained  on  other  media. 
Other  fluids  which  may  be  used  are  serum,  ascitic  fluid,  and  hydrocele 
fluid,  each  of  which  are  efficient  in  ordinary  conditions.  Loffler's 
serum  will  also  grow  the  organism,  but  not  so  freely  as  the  other  media. 
For  ordinary  purposes  a  medium  with  fresh  serum  added  to  it  is 
the  most  convenient,  and  such  a  medium  is  considerably  improved  if 
nutrose  is  added.  Another  substance  which  has  been  used  instead  of 
nutrose  is  legumin.  Nutrose  or  legumin  agar*,  with  fresh  serum  added 
to  it,  is  a  very  satisfactory  medium  for  working  with  on  plates,  as  it  is 
transparent,  and  any  colonies  growing  on  it  can  thus  be  easily  examined 
with  a  low  power  of  the  microscope.  This  is  an  important  matter  when 
searching  for  gram-negative  cocci  in  throat  swabs.  The  medium  is  also 
convenient  for  keeping  stock  cultures,  as  the  purity  of  cultures  in  tubes 
can  be  checked  by  the  low  power  of  the  microscope. 
*  See  Appendix  II  for  its  preparation. 


150  Bacteriology  [cH. 

Another  medium,  which  is  of  the  greatest  value  for  the  purpose  of 
keeping  stock  cultures,  is  a  corn-starch  medium  invented  by  Vedder, 
1  per  cent,  of  starch  being  added  to  ordinary  agar.  Its  value  consists 
in  the  fact  that  the  meningococcus  will  remain  alive  longer  upon  this 
medium  than  upon  any  of  the  media  already  described.  If  any  other 
medium  is  used,  the  only  safe  rule  is  to  sow  all  cultures  daily,  as  it  often 
happens  that  a  48  hours'  growth  fails  to  sub-culture;  with  the  starch 
medium,  however,  successful  sub-cultures  may  be  made  after  four  or 
even  five  days,  when  the  medium  is  used  in  the  form  of  a  slope.  If 
the  medium  is  used  in  the  form  of  a  stab,  the  vitahty  of  any  culture  is 
enormously  increased,  and  successful  sub-cultures  can  be  obtained  from 
a  five  or  six  weeks  old  growth.  It  is  always  safe  to  keep  such  cultures 
for  ten  days  before  resowing.  The  organism  is  a  strict  aerobe,  and 
therefore  only  grows  on  the  cup-like  surface  of  the  starch  stab ;  it  is 
remarkable  what  a  luxuriant  growth  can  be  obtained  from  a  culture 
which  looks  half  dried  up. 

For  the  purposes  of  sub-culture  it  is  essential  to  sow  thickly;  as 
much  of  the  culture  as  can  be  conveniently  carried  on  the  needle  should 
be  used.  No  difference  arises  in  this  respect,  whether  the  culture  to 
be  sown  shews  irregular  and  badly  staining  forms,  or  not.  The  reason 
for  this  peculiarity  is  not  easy  to  understand,  more  especially  in  the 
light  of  the  vigorous  culture  which  can  be  obtained  from  a  month  old 
starch  stab.  It  is  difficult  to  imagine  that  an  autolytic  ferment  is 
rapidly  formed,  which  only  a  few  individuals  can  survive;  for  if  this 
were  the  case,  the  stab  culture  should  die  out  even  more  rapidly  than 
a  slope  culture.  The  point  is  one  of  considerable  practical  importance, 
but  its  explanation  has  not  yet  been  given.  It  is  possible  that  physical 
conditions  are  the  determining  factor;  for  a  successful  sub-culture  is 
usually  impossible  on  a  serum  agar  slope  which  has  become  too  dry. 
A  starch  stab  may  owe  its  success  to  its  power  of  keeping  the  surface 
of  the  medium  at  just  the  right  condition  of  moisture.  In  fluid  culture 
growth  is  very  irregular.  It  can  at  times  be  obtained  in  an  ordinary 
peptone  broth  tube,  but  it  is  much  facilitated  by  the  addition  of  serum 
or  ascitic  fluid.  In  contrast  to  that  necessary  for  soUd  media,  the 
amount  of  such  fluid  that  must  be  added  is  considerable;  "5  c.c.  of 
serum  should  be  added  to  every  5  c.c.  of  medium.  The  reaction  of 
the  medium  is  important,  the  best  growth  being  obtained  sUghtly  on 
the  acid  side  of  the  neutral  point  of  phenol  phthalein.  Any  considerable 
variation  from  this  will  frequently  prevent  growth  from  taking  place. 
The  chief  importance  of  fluid  media  is  for  the  purpose  of  determining  the 


xi]  Bacteriology  151 

fermentative  power  of  a  given  organism  on  carbohydrates,  and  will  be 
further  discussed  in  deaUng  with  these  reactions.  In  milk  the  meningo- 
coccus grows  without  change  of  reaction  or  clotting. 

The  appearances  of  the  meningococcus  colony  on  such  a  medium  as 
nutrose  serum  agar  are,  to  a  certain  extent,  characteristic.  When 
examined  by  a  low  power  of  the  microscope,  the  colony  has  the  following 
characters  common  to  the  gram-negative  group  of  diplococci.  When 
24  hours  old  it  is  fairly  large,  smooth,  and  transparent,  with  a  regular 
circular  edge.  In  colour  it  is  one  of  the  hghtest  of  the  organisms  in 
the  group,  its  outer  zone  is  almost  colourless,  while  the  inner  part  is 
a  clear  hght  yellow.  In  older  cultures,  36  to  48  hours  old,  a  character- 
istic stipphng  appears  at  the  centre  of  the  colony,  the  innermost  zone 
becoming  covered  with  small  dark  spots;  the  colony  often  becomes 
concentrically  ringed,  an  appearance  due  in  all  probabihty  to  an 
alteration  in  the  rate  of  growth.  The  outer  edge  of  the  colony  may 
now  no  longer  be  circular,  but  may  be  irregularly  scolloped  owing  to 
the  more  vigorous  growth  of  certain  portions.  The  appearance  of  the 
colonies  to  the  naked  eye  is  also  somewhat  characteristic.  When 
viewed  by  transmitted  Ught,  they  are  semi-opaque,  and  have  a  bluish- 
grey  sheen,  which  is  in  marked  contrast  to  the  more  opaque  and  deeply 
pigmented  members  of  the  gram-negative  group.  Occasionally  a 
perfectly  pure  culture  shews  two  classes  of  colony  of  very  different  size, 
one  class  being  the  ordinary  large  colonies,  and  the  other  very  much 
smaller  ones;  the  appearance  is  such  as  to  give  rise  to  the  suspicion 
that  two  different  organisms  are  present.  We  have  many  times  picked 
out  the  various,  colonies,  examined  them,  sub-cultured  them,  and 
tested  them,  and  have  always  found  that  we  were  deahng  with  only 
one  organism.  The  difference  in  size  of  the  colonies  is  probably  due 
to  the  inhibition  of  some  organisms  for  a  certain  period  after  sowing, 
while  others  begin  to  prohferate  immediately.  The  evidence  is  against 
the  phenomenon  being  due  to  a  different  rate  of  growth,  for  sub-cultures 
from  the  two  forms  of  colony  grow  equally  well.  The  vitahty  of  the 
organism  in  culture  has  already  been  dealt  with,  and  varies  greatly 
according  to  the  medium  used,  its  length  of  Ufe  varying  from  24  hours 
to  over  six  weeks,  when  sohd  media  are  used ;  in  fluid  media  it  usually 
remains  ahve  for  a  week,  but  we  have  recovered  it  as  long  as  three 
weeks  after  sowing. 

Another  phenomenon  occurs  which  is  of  some  practical  importance, 
especially  when  sowing  from  cerebro-spinal  fluid.  Colonies  may  not 
appear  in  the  first  24  hours  of  incubation,  but  yet  be  found  two  or 


152  Bacteriology  [ch. 

three  days  after  sowing;  there  is  apparently  an  inhibition  of  the 
organism ;  it  does  not  die,  but  does  not  immediately  develop.  This 
inhibition  has  already  been  mentioned  as  the  most  probable  cause  of 
the  occurrence  of  large  and  small  colonies  in  one  culture.  It  is  the  rule 
when  cultures  are  kept  at  temperatures  between  20°  and  23°  C.  Though 
httle  or  no  growth  is  obtained  at  such  a  temperature,  a  luxuriant  growth 
appears  on  transferring  to  37°  C.  In  the  case  of  cultures  of  cerebro- 
spinal fluid,  it  is  not  merely  a  question  of  re-inoculation  of  the  slope 
with  the  condensation  fluid,  for  we  have  obtained  culture  for  the  first 
time  on  the  fifth  day  after  sowing,  though  our  practice  has  been  daily 
to  moisten  the  slope  afresh  with  condensation  fluid.  We  have  also 
found  colonies  shewing  on  the  second  or  third  day  only,  when  no  re- 
inoculation  with  condensation  fluid  has  been  done.  The  above  facts 
estabhsh  the  occurrence  of  a  true  inhibition,  which  varies  in  length 
with  different  circumstances.  This  inhibition  also  occurs  in  the  case  of 
plates  from  throat  swabs ;  these  should  therefore  always  be  kept  for 
48  hours. 

The  temperature  of  optimum  growth  is  36°  to  37°  C.  At  tempera- 
tures above  42°  C.  no  growth  takes  place.  A  temperature  of  65°  C.  for 
thirty  minutes  kills  the  meningococcus.  The  minimum  temperature  of 
growth  was  defined  by  Albrecht  and  Ghon  to  be  between  25°  and  27°  C. 
Some  of  our  strains,  however,  have  shewn  definite  growth  at  temperatures 
as  low  as  23°  C,  especially  if  grown  on  blood  agar.  As  already 
mentioned,  we  do  not  consider  that  the  test  of  growth  at  23°  C.  is  a 
certain  difi'erentiation  of  the  meningococcus  from  the  rest  of  the  group. 
It  is  true  that  usually  the  meningococcus  fails  to  shew  definite  growth 
on  nutrose  serum  agar  at  23°  C,  but  we  have  obtained  strains  from 
puncture  fluid  which  do  shew  a  certain  amount  of  growth  on  this 
medium  at  this  temperature ;  on  the  other  hand,  certain  other  members 
of  the  gram-negative  group  do  not  grow  any  better  than  the  meningo- 
coccus at  this  temperature. 

The  effect  of  sunhght  is  rather  surprising,  the  organism  being  very 
resistant  to  it.  Elser  and  Huntoon  found  that  some  strains  survived 
8  or  9  hours'  exposure;  we  have  found  strains  to  survive  7  hours' 
exposure.  All  our  strains  tested  survived  1  to  2  hours'  exposure  to 
full  sunhght. 

Desiccation,  on  the  other  hand,  has  a  marked  effect  in  killing  the 
meningococcus.  We  have  foimd  that  no  growth  could  be  obtained 
from  coversUps  smeared  with  meningococcus  cultures  after  flve  to  ten 
minutes'  desiccation  in  a  sulphuric  acid  desiccator.     When  dried  on 


xi]  Bacteriology  153 

glass  in  the  ordinary  air,  24  hours'  exposvire  has  been  found  by  various 
observers  to  destroy  the  organism.  Elser  and  Huntoon  devised  experi- 
ments, which  tend  to  shew  that  the  meningococcus  can  survive  somewhat 
longer  than  this  under  certain  circumstances.  The  difficulty  of  recovery 
of  the  whole  gram-negative  group  from  swabs,  which  have  been  kept  any 
considerable  time  before  sowing,  also  shews  that  these  organisms  are 
very  sensitive  to  drying. 

The  action  of  disinfectants  is  very  marked.  Weichselbaum  found 
that  carbohc  acid  diluted  to  1  in  800  prevents  growth,  and  that 
formaldehyde  diluted  to  1  in  22,500  rapidly  kills  the  organism. 

The  pathogenicity  of  the  meningococcus  with  regard  to  the  ordinary 
laboratory  animals  is  comparatively  shght.  Weichselbaum  found  that 
subcutaneous  injections  in  mice  or  guinea-pigs  produced  no  efEect. 
If,  however,  fairly  large  doses  of  an  agar  emulsion  were  injected  intra- 
peritoneally,  death  was  produced  in  from  36  to  48  hours.  The  peri- 
toneum was  found  to  be  filled  with  an  exudate  crowded  with  the 
organism,  which  was  especially  to  be  foimd  inside  the  bodies  of  leucocytes. 
He  also  produced  a  fatal  result  by  intravenous  inoculation  in  the 
rabbit;  sub-dural  inoculation  in  this  animal  produced  doubtful  results. 
Sub-dural  inocidation  in  the  dog,  however,  in  one  case  produced 
a  purulent  meningitis  fatal  in  twelve  days,  from  which  he  could 
not  recover  the  meningococcus;  in  another  case,  which  was  fatal 
within  24  hours,  he  -was  able  to  recover  the  organism.  Councilman, 
Mallory  and  Wright  claim  to  have  succeeded  in  producing  meningitis 
in  the  goat  by  injecting  the  meningococcus  into  the  spinal  canal.  The 
classical  experiments  are,  however,  those  of  von  Lingelsheim  on  the 
monkey.  He  introduced  the  meningococcus  intra-spinally  into  two 
monkeys,  the  first  of  these  developed  rigidity  of  the  neck  and  of  the 
dorsal  muscles,  and  had  attacks  of  vomiting;  this  acute  condition 
lasted  six  days,  and  then  gradual  recovery  took  place.  The  other 
monkey,  a  snialler  animal,  developed  more  severe  symptoms,  and  died 
in  30  hours  with  a  purulent  exudation  of  the  brain  and  cord,  from  which 
the  meningococcus  was  recovered.  Similar  results  have  been  obtained 
by  Flexner  and  Stuart  McDonald;  other  observers  have,  however, 
obtained  negative  results.  All  attempts  to  reproduce  meningitis  in 
animals  by  introducing  the  organism  into  some  other  part  of  the 
body  have  failed,  experimental  evidence  for  a  haematogenous  origin  of 
the  disease  is  thus  entirely  lacking.  Too  much  stress  should  not  be  laid 
on  the  reproduction  of  the  disease  in  animals  by  sub-dural  or  intra- 
spinal inoculation,  for  a  large  number  of  organisms  will  do  the  same, 


154  Bacteriology  [ch. 

many  of  which  are  never  found  to  be  the  causes  of  meningitis  occurring 
in  the  human  body.  It  is,  however,  a  matter  of  some  importance  that 
an  organism  of  such  low  virulence  can  reproduce  the  essentials  of  the 
disease  in  animals. 

The  toxins  produced  by  the  meningococcus  have  been  investigated 
by  Albrecht  and  Ghon  and  by  Rist  and  Paris;  they  have  been  unable 
to  find  evidence  of  an  extra-cellular  toxin  when  the  meningococcus  has 
been  grown  in  fluid  media.  Albrecht  and  Ghon  further  found  that  the 
intraperitoneal  injection  of  a  killed  culture  in  a  white  mouse  killed 
the  animal  in  the  same  way  as  the  injection  of  a  hve  culture  did,  they 
therefore  considered  that  the  pathological  action  of  the  organism  was 
due  mainly  to  an  endotoxin.  In  man,  it  is  questionable  whether  a 
toxic  effect  is  a  large  factor  in  the  disease.  It  has  already  been  explained 
that  most  of  the  symptoms  can  be  attributed  to  the  local  invasion  of 
the  cerebro-spinal  system,  and  the  increase  of  intracranial  pressure 
which  accompanies  this.  The  heart  is  essentially  the  organ  which  is 
affected  by  any  toxic  process;  but  the  alterations  in  the  pulse  in  this 
disease  depend  more  upon  the  cerebral  condition  than  upon  any  direct 
effect  on  the  cardiac  muscle.  Heart  failure  is  not  a  comphcation  which 
need  be  guarded  against,  and  no  evidence  of  failure  of  the  cardiac 
muscle  is  found  post-mortem.  As  the  pathogenic  power  of  the  meningo- 
coccus in  laboratory  animals  is  so  small,  it  is  of  no  value  for  differen- 
tiating the  meningococcus  from  micrococcus  catarrhalis  and  the 
non-pathogenic  gram-negative  diplococci.  Even  the  reproduction  of 
meningitis  is  of  httle  value  and  is  apparently  uncertain. 

The  cultural  characteristics  of  the  other  gram-negative  diplococci 
have  already  been  stated  not  to  be  sufficiently  distinctive  to  enable 
the  differentiation  to  be  made  on  these  grounds  alone.  Certain 
characteristics,  however,  are  fairly  constant  in  each  group,  and  are 
sufficiently  distinct  to  enable  anyone,  who  is  constantly  dealing  with 
them,  to  make  a  fairly  accurate  guess.  The  non-pathogenic  gram- 
negative  diplococci  found  in  the  throat  will  be  first  described,  and  then 
micrococcus  catarrhalis,  which  has  some  pathogenic  power. 

The  non-pathogenic  group  consists  of  micrococcus  pharyngis  siccus 
and  the  chromogenic  or  flavus  group. 


xi]  Bacteriology  155 

Micrococcus  Fliaryngis  Sicciis. 

This  organism  was  first  described  by  von  Lingelslieim.  It  is  the 
smallest  of  the  gram-negative  diplococci  and  is  usually  very  regular; 
it  stains  well  and  uniformly  with  methylene  blue.  In  old  cultures 
it  may  shew  badly  staining  and  irregular  forms,  but  this  is  on 
the  whole  more  unusual  with  this  organism  than  with  any  others 
in  the  group.  When  stained  by  Gram's  method,  it  is  entirely  gram- 
negative  when  first  obtained,  and  also  in  sub-cultures  when  young; 
in  older  sub-cultures  it  very  commonly  shews  a  considerable  number 
of  gram-positive  forms ;  it  produces  these  forms  much  more  easily 
than  any  other  of  the  gram-negative  diplococci.  Its  cultural  character- 
istics shew  that  it  is  the  most  vigorous  of  all  these  organisms.  It 
grows  comparatively  well  on  ordinary  agar,  and  can  be  kept  ahve  in 
sub-culture  on  this  medium :  it,  however,  grows  best  on  the  media 
which  have  been  described  as  suitable  for  the  growth  of  the  meningo- 
coccus, such  as  blood  agar  and  nutrose  serum  agar.  It  grows  freely 
in  fluid  media,  but  best  in  such  media  with  serum  or  ascitic  fluid  added. 
On  nutrose  serum  agar  it  grows  as  a  white  coalescent  growth,  which 
soon  becomes  adherent  to  the  medium.  This  adherence  commences  as 
a  skin  over  the  colonies,  which  can  be  torn  with  a  needle  and  the  soft 
centre  of  the  colony  easily  removed;  later,  however,  it  may  become 
so  dry  and  adherent  as  to  be  extremely  difficult  to  remove.  If  sub- 
culture is  persisted  in  for  some  weeks,  many  strains  lose  these  character- 
istics, they  become  much  less  adherent  and  no  longer  form  a  skin; 
ultimately  they  may  become  so  paint-hke  as  to  resemble  fairly  closely 
a  culture  of  the  meningococcus.  Their  rather  dense  white  appearance 
also  becomes  lost,  and  they  become  much  more  transparent.  The 
individual  colony  under  the  low  power  of  the  microscope  is  a  deep 
orange  yellow,  without  any  clearer  marginal  zone.  After  continued 
sub-culture,  when  the  above  described  alterations  have  taken  place,  the 
colonies  may  be  quite  pale,  shewing  a  light  yellow-brown  colour  mainly 
in  their  centre.  This  organism  may  occasionally  shew  large  and  small 
colonies  hke  those  in  the  meningococcus  cultures.  The  vitahty  of  the 
organism  is  very  similar  to  that  of  the  rest  of  the  group ;  sub-cultures 
should  be  made  every  two  days  on  slopes ;  in  starch  stabs  the  organism 
remains  ahve  for  weeks.  The  growth  at  23°  C.  is  important ;  strong 
growth  takes  place  at  this  temperature,  bxit  very  often  only  parts  of 
the  smear  on  the  surface  of  the  slope  will  grow.  It  is  necessary  for 
this  test  as  well  as  in  sub-culture  to  sow  fairly  thickly. 


156  Bacteriology  [cH. 

The  chromogenic  or  flavus  group  has  been  divided  in  various  ways 
by  different  observers.  In  our  experience  three  different  organisms 
have  been  met  with,  which  can  be  divided  according  to  the  table  on 
page  145. 

Micrococcus  Flavus  I. 
The  fermentative  properties,  on  which  this  organism  is  separated, 
will  be  referred  to  later.  Its  morphological  characters  are  very  hke 
those  of  the  preceding  organism.  In  culture,  the  cocci  are  usually 
fairly  regular  in  size  and  staining  power,  being  on  the  whole  smaller 
than  the  average  size  of  the  meningococcus.  In  old  cultures  it  fairly 
often  shews  irregularities  in  size  and  staining  power.  With  respect  to 
Gram's  stain,  it  hardly  ever  shews  gram-positive  forms,  even  in  very 
old  cultures.  It  is  a  strongly  growing  organism  on  the  special  media 
already  described,  and  can  be  kept  alive  for  some  time  on  plain  agar. 
In  fluid  media  some  strains  are  more  difficult  to  grow  than  others,  but 
none  grow  as  easily  as  pharyngis  siccus.  The  growth  on  sohd  media 
takes  the  form  of  rather  dry  colonies,  which  do  not  coalesce  very  easily, 
and  can  be  moved  about  over  the  surface  of  the  medium  with  a  needle. 
In  some  strains,  however,  these  characteristics  are  not  conspicuous, 
and  the  growth  tends  to  coalesce  into  a  stringy  mass,  which  is  very 
adherent  to  the  needle  when  picked  up.  Occasionally  large  and  small 
colonies  are  met  with  in  a  culture.  The  colour  of  the  growth  is  an 
orange  yellow,  the  depth  of  tint  varying  considerably  in  different  strains, 
and  in  any  particular  strain  on  different  media.  Under  the  low  power 
of  the  microscope  the  colonies  are  a  clear  orange  yellow  with  no  relative 
paleness  of  the  outer  zone.  The  minimum  temperature  of  growth  is 
considerably  below  23°  C,  so  that  the  organism  grows  strongly  at  this 
temperature;  a  culture  equal  to  a  24  hours'  culture  at  37°  C.  is  usually 
obtained  in  48  hours. 

Micrococcus  Flavus  II. 
This  organism  is  morphologically  hke  M.  flavus  I,  but  is  usually 
somewhat  smaller  in  size.  It  has  rather  more  tendency  towards  badly 
staining  and  irregular  forms.  Gram-positive  forms  are  rarely  met  with. 
Its  growth  on  special  media  is  much  less  vigorous  than  that  of  flavus  I, 
the  colonies  are  usually  smaller  and  more  transparent,  being  of  a  pale 
orange  colour.  On  ordinary  agar  it  grows  very  poorly.  In  fluid  media 
it  usually  grows  fairly  well,  but  rather  slowly.  It  occasionally  shews 
on  solid  media  large  and  small  colonies.  The  colony  under  the  low 
power  is  very  similar  to  that  of  flavus  I,  but  is  usually  smaller  and  less 


xij  Bacteriology  157 

deeply  coloured.  At  23°  C.  the  coccus  may  or  may  not  shew  shght 
signs  of  growth,  usually  growth  is  for  practical  purposes  absent ;  23°  C. 
can  thus  be  taken  to  be  just  below  the  minimum  temperature  of  growth. 
It  is  therefore  in  this  respect  very  similar  to  the  meningococcus. 

Micrococcus  Flavus  III. 
This  organism  is  morphologically  similar  to  flavus  I  and  II ; 
it  however  more  frequently  shews  irregular  and  badly  staining  forms. 
Gram-positive  forms  are  occasionally  met  with.  With  regard  to  its 
cultural  characteristics,  it  usually  grows  well  on  special  media,  but 
poorly  on  plain  agar.  The  growth  tends  to  coalesce,  and  is  paint-hke 
in  an  organism  freshly  obtained  from  the  throat.  After  continued 
sub-culture,  it  usually  tends  to  become  sticky.  Its  colour  differs 
somewhat  from  that  of  flavus  I  or  II;  it  is  more  of  a  canary 
yellow,  contrasting  with  the  orange  yeUow  of  the  other  two.  Under 
the  low  power  the  colonies  are  orange  yellow  and  often  have  a  less 
coloured  outer  zone.  It  usually  grows  fairly  easily  in  fluid  media, 
occasionally  however  a  particular  strain  is  difhcult  to  cultivate  in  them. 
In  common  with  the  others  of  the  flavus  group,  it  is  necessary  to 
sub-culture  every  two  days  to  be  certain  of  keeping  a  strain  ahve. 
With  regard  to  growth  at  23°  C.  two  classes  are  met  with,  one  which 
grows  quite  well  at  this  temperature,  the  other  which  fails  to  grow. 
For  convenience  the  group  flavus  III  may  be  subdivided  into  III  A 
growing  strongly  at  23°  C,  and  III  B  not  growing  at  this  temperature. 

Micrococcus  Catarrhalis. 

With  regard  to  its  morphology  this  organism  partakes  more  of  the 
nature  of  the  meniugococcus  than  of  the  non-pathogenic  members  of 
the  group.  It  is  usually  rather  a  larger  organism  than  those  which 
have  just  been  described,  and  more  frequently  shews  badly  staining 
forms  and  irregularities  in  size  and  shape.  It  is  usually  entirely  gram- 
negative,  but,  more  rarely  than  in  the  case  of  the  meningococcus, 
gram-positive  forms  are  occasionally  seen  in  an  old  culture.  The 
organism  grows  strongly  and  rapidly  on  special  media,  and  fairly  on 
ordinary  agar.  The  growth  on  nutrose  serum  agar  soon  becomes  con- 
fluent, and  is  very  similar  in  appearance  to  that  of  a  strongly  growing 
meningococcus.  Its  consistency  is  also  similar,  being  paint-hke  and 
easily  picked  up  with  a  needle.  It  is  perhaps  not  quite  so  transparent 
as  the  meningococcus,  but  there  is  very  httle  difference  in  this  respect. 
The  individual  colony  is  also  very  hke  the  meningococcus  colony  under 


168  Bacteriology  [CH. 

the  low  power,  it  is  of  a  light  yellow  colour  with  a  pale  peripheral  zone. 
In  our  experience  it  does  not  differ  greatly  in  size  from  the  colony  of 
the  meningococcus.  In  fluid  cultures  it  grows  quite  readily.  At 
23°  C.  very  little  development  takes  place ;  some  of  our  strains  entirely 
failed  to  grow.  This  organism,  therefore,  very  closely  resembles  the 
meningococcus  in  its  morphological  and  cultural  characters,  the  main 
difference  between  them  is  that  M.  catarrhalis  grows  more  freely. 

For  the  purposes  of  studying  sugar  reactions,  we  have  kept  a  number 
of  strains  of  the  above  groups  for  some  months.  Testing  them  at 
intervals  we  have  found  that  the  power  to  grow  in  the  cold  at  23°  C. 
ultimately  becomes  lost  throughout  the  group,  the  organisms  which 
retain  the  power  to  grow  at  this  temperature  longest  belong  to  the 
flavus  I  group,  but  even  these  finally  fail  to  develop  after  some  months' 
cultivation  at  37°  C. 

The  fermentation  reactions  of  the  gram-negative  diplococci  have 
been  in  the  main  rehed  upon  for  differentiation.  We  have  studied  the 
fermentation  reactions  of  particular  strains  for  months,  and  have  found 
them  remarkably  constant.  The  fundamental  difficulty,  in  making  use 
of  these  reactions  for  the  purpose  of  differentiation,  is  the  comphcated 
nature  of  the  medium  which  has  to  be  used,  and  the  difficulty  of 
efficiently  sterilizing  it  without  causing  alterations  in  the  sugar  present. 
Not  only  have  we  found  that  htmus  used  as  an  indicator  may  become 
discoloured,  so  as  to  be  practically  useless,  at  the  end  of  sterihzation, 
but  we  have  also  made  media  which  withstood  the  sterihzation  process 
fairly  well,  but  then  altered  in  colour  when  incubated  at  37°  C.  This 
latter  alteration  occurs  particularly  easily  with  certain  samples  of 
glucose,  it  is  therefore  essential  to  use  only  a  satisfactorily  tested 
glucose.  Other  sugars  which  are  also  difficult  to  sterilize  satisfactorily 
are  galactose,  laevulose  and  mannose,  and  the  discordant  results  of 
various  observers  on  the  fermentation  of  these  sugars  by  the  gram- 
negative  diplococci  are  due  to  this  difliculty.  The  matter  is  the  more 
important,  since  the  meningococcus  and  some  other  members  of  the 
group  take  some  days  to  shew  with  certainty  their  fermentative  power, 
and  the  terminal  reaction  may  be  only  comparatively  shght.  It  is 
therefore  always  necessary  to  work  with  an  uninoculated  control  tube. 
A  series  of  tubes  prepared  without  the  proper  precautions  may  give 
all  sorts  of  results,  so  that  organisms  may  be  considered  to  ferment 
a  particular  sugar  owing  to  a  reaction  which  the  tube  alone  would  give, 
if  incubated  without  inoculation.     Elser  and  Huntoon  have  investigated 


xi]  Bacteriology  159 

the  matter  very  thoroughly,  and  have  proved  that  some  of  the  reactions 
recorded,  such  as  that  of  the  fermentation  of  galactose  by  the  meningo- 
coccus and  others,  are  entirely  due  to  this  difficulty  of  preparation. 
We  have  also  investigated  the  matter  at  some  length  and  completely 
endorse  the  views  of  Elser  and  Huntoon.  These  authors  recommend 
the  employment  of  a  sohd  medium  tinted  with  htmus  and  with  the 
sugar  incorporated  in  it;  they  bring  forward  various  objections  to  the 
use  of  fluid  media.  Some  of  their  objections  are  in  our  opinion 
advantages,  such,  for  instance,  as  the  greater  length  of  time  required 
for  a  definite  reaction  to  shew,  and  also  the  necessity  for  sub-culture 
from  a  fluid  medium  to  test  growth  and  purity  of  sowing.  The  length 
of  time  taken  is  characteristic  of  certain  organisms,  and  it  is  much 
easier  to  be  certain  of  the  presence  or  absence  of  contamination  when 
sowing  from  a  fluid  medium.  In  our  hands  the  use  of  such  solid  media 
has  never  given  such  definite  results  as  can  be  obtained  by  using  fluid 
media.  When  such  deUcate  reactions  are  being  tested,  that  method 
which  gives  the  most  definite  result  is  essential. 

We  endeavoured  to  increase  the  rapidity  of  obtaining  a  positive 
reaction  by  making  use  of  neutral  red  as  an  indicator  instead  of  litmus. 
By  this  means  a  reaction  is  shewn  about  twice  as  quickly  as  when 
htmus  is  used;  we  found,  however,  that  the  more  shghtly  reacting 
organisms,  such  as  the  meningococcus  and  some  members  of  the  flavus 
group,  gave  a  reaction  far  too  indeterminate  to  be  of  great  value.  The 
use  of  this  indicator  was  therefore  abandoned. 

The  medium  that  we  have  used  has  been  made  in  the  following 
way.  Veal  broth  is  made  in  the  ordinary  way,  soaking  the  veal  for 
two  hours ;  to  this  is  added  1  per  cent,  peptone  and  -5  per  cent,  sodium 
chloride.  The  mixture  is  then  made  -1-  -2  acid  to  phenol  phthalein  with 
sodium  hydrate,  and  Htmus  is  added  so  as  to  produce  a  strong  blue  in 
a  test  tube  of  the  mixture.  We  have  found  it  necessary  to  add  enough 
Htmus  to  produce  this  strong  colour,  as  the  process  of  steriHzation  may 
practically  destroy  the  colour,  if  the  Htmus  is  too  weak.  The  sugar, 
whose  fermentation  is  to  be  tested,  is  added  so  as  to  form  a  1  per  cent, 
solution.  The  medium  with  sugar  added  is  now  submitted  to  steriHza- 
tion in  the  steamer  for  half  to  three-quarters  of  an  hour  on  three 
successive  days,  it  is  then  tubed  off,  fresh  serum  being  added  in  the 
proportion  of  -5  c.c.  to  every  5  c.c.  tube. 

We  have  also  made  use  of  another  mixture,  which  has  the  advantages 
that  it  can  be  completely  steriHzed,  and  that  no  fresh  body  fluid  is 
contained  in  it.     This  medium  was  elaborated  and  tested  by  Vines  in 


160  Bacteriology  [cii. 

the  laboratory  of  the  First  Eastern.  General  Hospital.  It  is  made  up 
in  the  same  way,  but  1  per  cent,  cornflower  starch  is  added  to  the 
mixture  in  its  first  stage  before  sterihzation.  It  has  been  found  that 
all  reactions  can  be  obtained  in  this  medium  without  the  addition  of 
fresh  serum,  and  that  it  alters  very  little  during  sterihzation.  Elser 
and  Huntoon  have  gone  thoroughly  into  the  question  of  the  necessity 
of  using  carefully  prepared  media  with  the  right  reaction.  They  have 
shewn  that  many  of  the  recorded  observations  on  the  fermentation  of 
sugars  by  the  meningococcus  are  erroneous,  the  reaction  obtained 
having  been  due  to  alterations  in  a  badly-prepared  medium.  Not  only 
is  the  difficulty  of  obtaining  a  good  colour  for  a  sterilized  medium  due 
to  neglect  of  the  above  precautions,  but  media  may  also  be  obtained 
which  change  colour  in  the  incubator,  though  apparently  satisfactory 
when  sterilization  is  complete.  This  may  give  rise  to  the  view  that 
a  fermentation  has  taken  place  due  to  the  inoculated  organism,  when 
in  reahty  the  alteration  is  due  to  the  medium  alone.  We  have  also 
worked  with  still  another  medium,  namely.  His'  medium  with  htmus 
as  indicator.  It  is  a  medium  which  is  difficult  to  get  good  in  colour, 
and  in  which  the  fermentative  changes  are  sometimes  rather  indefinite. 
We  have  found  that  this  medium  is  not  so  certain  with  respect  to  the 
growth  of  the  inoculated  organism  as  the  two  media  described  above. 

The  fermentation  reactions  of  the  gram-negative  diplococci  are 
shewn  in  the  following  table: 

Glucose  Maltose  Manuose  Laevulose  Saccharose   Lactose  Galactose  Mannite  Dulcite  Dextrin  Inuliu 

M.  pharyngis       H-++             +  +  --  ____ 

siccus 

M.  flavus  I+++            4-  +  -          -  ____ 

M.  flavus  II         +        ++            +  -1-  --  __-_ 

M.  flavus  III+--I-+            +  -  --  ____ 
Meningoooccus  ^ 

Para-meningo-  f++-             -  -  --  ____ 

coccus  -' 

Gonoooocus         -I---            -  -  --  ____ 

M.  catarrhalis      ___-  -  --  ____ 

It  will  be  seen  that  none  of  these  organisms  ferments  lactose,  galactose, 
dextrin,  mannite,  dulcite  or  inuhn.  Their  differentiation  therefore 
depends  upon  their  effect  upon  dextrose,  maltose,  mannose,  laevulose 
and  saccharose.  With  the  exception  of  the  gonococcus  and  micrococcus 
catarrhalis,  all  these  organisms  ferment  glucose  and  maltose.  As  the 
differentiation  of  the  gonococcus  from  the  meningococcus  need  not  be 
considered  in  dealing  with  the  cocci  of  the  throat,  it  is  unnecessary  to 


XI  j  Bacteriology  16  J 

use  more  than  one  of  these  two  sugars.  Similarly,  it  will  also  be  seen 
that  the  reactions  to  mannose  and  laevulose  are  similar.  Here  again, 
only  one  of  these  need  be  employed;  laevulose  has  been  selected,  as 
it  reacts  more  rapidly  and  definitely  than  mannose.  We  have  made 
use  of  ghicose,  laevulose  and  saccharose  for  differentiation.  Throughout 
the  group  the  reaction  with  glucose  is  usually  the  most  rapid,  the 
htmus  therefore  first  changes  colour  in  the  glucose  tube ;  it  is,  however, 
necessary  to  keep  the  other  sugars  after  a  reaction  has  been  obtained 
in  the  glucose  tube,  as  they  may  ultimately  also  change.  It  is  absolutely 
necessary  to  sub-culture  from  the  sown  tube,  to  make  sure  that  growth 
has  taken  place,  and  that  no  contamination  has  been  sown.  The 
latter  point  is  extremely  important,  and  in  some  cases  very  difficult  to 
avoid  when  dealing  with  cultures  from  the  throat ;  it  is  sometimes  almost 
impossible  to  separate  the  suspected  organism  from  the  large  numbers 
of  streptococci  which  also  grow  with  great  vigour  on  the  media  employed. 
These  streptococci  aU  turn  the  sugar  media  with  great  rapidity,  so 
that  the  only  confusion  that  can  arise  is  between  a  piire  culture  of 
M.  pharyngis  siccus,  and  a  culture  of  some  other  gram-negative  diplo- 
coccus  contaminated  with  a  streptococcus. 

The  reactions  of  the  various  members  of  the  group  have  already 
been  given  when  describing  our  classification,  it  is  therefore  unnecessary 
to  repeat  them  here.  The  reactions  of  the  meningococcus  and  para- 
meningococcus, which  are  both  the  most  doubtful  and  the  most  difficult, 
may  however  be  described  a  httle  more  fully.  In  the  table  it  has  been 
stated  that  the  meningococcus  ferments  glucose  and  maltose  only,  and 
this  is  in  all  probabihty  the  fact ;  we  have,  however,  on  various  occasions 
found  that  a  comparatively  shght  but  nevertheless  distinct  acidity 
may  temporarily  occur  at  the  third  or  fourth  day  in  both  mannose 
and  laevulose.  This  shght  acidity  then  disappears,  and  has  com- 
pletely vanished  on  the  seventh  day.  At  any  particular  stage  in 
the  test,  the  reaction  is  much  shghter  than  that  with  any  of  the 
others ;  it  is,  however,  quite  distinct.  In  tubes  in  which  good  growth 
has  taken  place,  marked  alkahnity  appears  at  the  end  of  a  week  when 
testing  mannose,  laevulose  and  saccharose.  The  glucose  reaction  varies 
considerably  with  difi'erent  strains  of  the  meningococci,  some  of  these 
not  only  shew  quicker  reaction,  but  also  ultimately  produce  a  more 
marked  acidity.  We  have  studied  for  some  months  a  strain,  obtained 
by  lumbar  puncture,  which  completely  failed  to  shew  acidity  in  glucose 
.  tubes.  Ultimately,  however,  after  prolonged  sub-culture  we  found  that 
the  organism  could  produce  a  sUght  degree  of  acidity.     In  the  slowly 

F.  &G.  11 


162  Bacteriology  [CH. 

developing  fermentation  reaction  of  the  meningococcus,  two  factors  are 
present,  the  production  of  acidity  by  the  fermentation  of  the  glucose, 
and  the  production  of  alkalinity  by  proteolysis.  In  the  strain  in  question 
this  production  of  alkali  was  much  more  rapid  than  in  other  strains 
tested  at  the  same  time,  it  is  probable  therefore  that  the  acid  produced 
by  fermentation  was  masked  by  the  alkaU  produced  by  proteolysis. 

Micrococcus  catarrhaUs  is  said  not  to  ferment  any  sugars ;  we  have, 
however,  found  that  indications  of  acidity  may  be  observed  on  the 
second  or  third  day  in  a  glucose  tube  sown  with  this  organism,  even 
when  htmus  is  used  as  an  indicator ;  if  neutral  red  be  used,  the  indication 
is  still  more  obvious.  Shortly  after  this,  on  the  fourth  day,  the  tube 
becomes  strongly  alkaUne.  It  is  possible  that  here  also  a  balanced 
reaction  is  taking  place,  but  that  the  alkaU  production  is  usually  so 
strong  and  rapid  as  to  overwhelm  the  slight  acidity  produced.  The 
practical  point  is  to  recognize  that  a  faint  acidity  may  be  seen  in  glucose 
with  M.  catarrhahs  on  the  second  or  third  day,  but  that  this  is  rapidly 
replaced  by  an  alkaUne  reaction.  There  is  therefore  httle  difficulty  in 
recognizing  M.  catarrhaUs.  We  have  also  met  with  an  organism 
belonging  to  the  group  we  call  flavus  III,  which  has  the  power  of  forming 
alkaU  very  rapidly;  with  this  organism  in  favourable  media  the  acid 
reaction  in  glucose  is  always  clear,  but  in  certain  samples  of  medium 
we  have  found  that  the  acid  reaction  is  almost  completely  masked, 
a  faint  acidity  on  the  second  day  being  rapidly  followed  by  a  strong 
alkahnity.  It  is  therefore  very  necessary  to  work  with  a  medium 
which  is  as  constant  as  possible,  and  for  this  reason  media,  to  which 
fresh  serum  is  added,  have  considerable  drawbacks.  It  is  possible  that 
the  starch  medium  already  described  may  prove  a  more  constant  and 
therefore  a  more  efficient  medium. 

When  the  question  of  the  differentiation  of  the  gram-negative 
diplococci  of  the  throat  first  arose,  high  hopes  were  entertained  that 
methods  of  agglutination  would  prove  successful  in  differentiating  the 
meningococcus  from  the  other  members  of  the  group.  EarUer  workers 
endeavoured  to  substantiate  distinctive  agglutination  reactions. 
Bettencourt  and  Fran9a  and  Weichselbaum  and  Gohn  found  in 
cerebro-spinal  fever  patients  a  considerable  increase  in  agglutinating 
power  above  that  of  the  serum  of  normal  persons;  they  obtained 
positive  agglutination  at  dilutions  varying  between  1  in  10  and  1  in 
100.  Albrecht  and  Gohn  first  obtained  experimentally  a  serum  with 
increased  agglutinating  power  by  inoculating  rabbits  with  meningo- 
coccus cultures.     The  first  extensive  investigation  of  the  gram-negative 


xi]  Bacteriology  163 

cocci  of  the  naso-pharynx  was  carried  out  by  Dunham,  who  not 
only  shewed  that  the  meningococcus  could  be  differentiated  from 
micrococcus  catarrhalis  by  its  power  of  fermenting  glucose,  but  also 
endeavoured  to  separate  these  organisms  by  using  agglutination  tests. 
He  made  use  of  the  microscopical  method  and  found  that  a  period  of 
24  to  48  hours  was  frequently  necessary  before  agglutination  became 
obvious.  He  found,  however,  that  even  then  the  increase  in  aggluti- 
nating power  was  not  sufficiently  great  to  overcome  the  possible  errors 
in  technique.  The  animals  he  used  were  rabbits,  a  goat,  a  horse,  and 
several  geese.  The  difficulties  of  technique  arise  not  only  in  preparing 
a  satisfactory  emulsion,  which  is  almost  impossible  with  certain  organisms 
of  the  group,  but  also  in  the  length  of  time  the  reaction  takes,  and 
the  uncertainty  of  obtaining  a  really  highly  agglutinating  serum.  The 
agglutinating  power  of  normal  serum  from  various  animals  is  very 
variable,  not  only  in  different  kinds,  but  also  in  different  individuals 
of  the  same  kind.  A  very  marked  difference  from  the  normal  must 
be  obtained  to  be  of  any  value.  Since  the  work  of  Dunham,  other 
observers  have  endeavoured  to  obtain  definite  results,  both  by  the 
microscopic  and  the  macroscopic  method,  but  without  conspicuous 
success.  The  macroscopic  method  is  less  troublesome  and  on  the 
whole  more  reUable.  The  mixture  of  emulsion  and  diluted  serum  is 
drawn  up  into  a  rough  capillary  pipette,  such  as  is  used  for  taking  blood 
for  examination,  and  sealed  off.  It  is  incubated  in  the  upright  position 
in  the  37°  C.  incubator.  The  measure  of  the  completeness  of  the 
reaction  is  furnished  by  two  indications.  Of  these  the  first  is  the 
deposit  of  the  agglutinated  cocci  in  the  lower  capillary  part  of  the  tube. 
The  second  concomitant  change  is  the  clearing  of  the  fluid.  The 
reaction  can  only  b?  considered  complete  when  the  fluid  becomes 
perfectly  clear;  it  takes  even  longer  than  when  the  microscopic 
method  is  used,  it  may  take  four  days  to  become  complete.  Another 
difficulty  also  arises  with  the  macroscopic  method ;  certain  organisms, 
notably  M.  catarrhahs,  undergo  autosedimentation.  It  is  therefore 
always  necessary  to  work  with  controls. 

Elser  and  Huntoon  have  exhaustively  studied  the  agglutination 
reactions  of  the  gram-negative  diplococci  and  more  especially  of  the 
meningococcus.  They  find  a  very  great  variation  in  the  power  to 
agglutinate  in  various  meningococcus  strains,  some  of  them  not  aggluti- 
nating even  in  the  lowest  dilutions.  These  inagglutinable  strains, 
however,  produced  sera  which  would  agglutinate  agglutinable  strains  at 
high  dilutions,  although  such  sera  had  no  power  to  agglutinate  their 

11—2 


164  Bacteriology  [CH. 

own  strains.  There  is  thus  an  additional  complication,  in  that  some 
strains  are  agglutinable,  and  some  inagglutinable.  Again,  group 
agglutinations  are  often  conspicuous,  a  meningococcus  serum  for 
instance  having  a  marked  agglutinating  power  on  the  gonococcus, 
and  vice  versa.  They  conclude  that  agglutinating  reactions  alone  are 
of  little  value  for  ordinary  diagnostic  purposes,  although  differentiation 
is  distinct  if  agglutinable  strains  are  dealt  with.  They  find,  however, 
that  absorption  tests  will  differentiate  the  various  groups  satisfactorily ; 
even  the  inagglutinable  strains  of  meningococci  shewing  marked 
absorptive  power.  Their  test  was  carried  out  as  follows:  a  standard 
suspension  of  the  organism  to  be  tested  was  made,  and  was  thoroughly 
mixed  with  an  equal  part  of  the  immune  serum,  against  which  it  was 
to  be  tried ;  control  tubes  were  also  made  with  salt  solution  in  the  place 
of  the  standard  suspension.  These  were  then  incubated  at  37°  C.  for 
two  hours.  This  was  found  to  be  long  enough,  as  no  further  absorption 
took  place  after  that  time.  The  tubes  were  then  centrifugahzed  for 
fifteen  minutes.  The  supernatant  fluid  was  pipetted  off,  and  agglutina- 
tion tests  carried  out  in  the  usual  manner  with  the  fluids  from  both 
tubes.  By  this  method,  the  treatment  of  an  immune  serum  by  an 
organism,  which  belongs  to  the  same  group  as  the  organism  used  for 
immunizing,  will  remove  the  agglutinating  power  of  that  serum  to  the 
immunizing  organism;  whereas,  if  the  organism  to  be  tested  does  not 
belong  to  the  same  group  as  the  immunizing  organism,  the  serum  will 
have  lost  none  of  its  agglutinating  power  over  the  latter. 

Elser  and  Huntoon  tested  by  these  methods  a  large  number  of 
meningococcus  strains,  some  of  which  were  agglutinable  and  some 
inagglutinable ;  they  also  tried  a  considerable  number  of  other  gram- 
negative  diplococci.  They  proved  that  this  absorption  reaction  was 
without  exception  rehable  for  the  differentiation  of  the  group ;  specific 
agglutinins  were  only  absorbed  by  members  of  the  same  species,  never 
by  members  of  another  species.  Only  in  one  meningococcus  strain  did 
the  absorption  of  the  specific  agglutinin  fail  to  take  place,  all  other 
strains,  with  very  various  agglutinating  capacities,  were  able  to  absorb 
their  specific  agglutinin.  We  may  therefore  conclude  from  their 
exhaustive  experiments  that  the  absorption  test  is  a  specific  reaction 
of  great  value  in  differentiation.  With  regard  to  simple  agglutinating 
experiments,  specific  agglutinating  reactions  can  undoubtedly  be 
demonstrated,  but  there  are  so  many  factors  to  be  taken  into  account, 
such  as  the  occurrence  of  agglutinable  and  inagglutinable  strains  of 
the   same   organism,   large  variations  in   the   agglutinating   power  of 


xi]  Bacteriology  165 

normal  seriun,  and  actual  technical  difficulties  in  performing  the  tests, 
as  to  render  simple  agglutination  experiments  quite  unrehable  for  use 
as  a  routine  method. 

Gordon,  has  also  studied  the  agglutinations  of  the  gram-negative 
diplococci  at  some  length,  and  has  arrived  at  the  conclusion  that  the 
present  position  of  our  knowledge  renders  simple  agglutinations  of 
httle  value.  He,  however,  confixms  the  contention  of  Elser  and  Huntoon 
that  definite  results  can  be  obtained  by  means  of  absorption  tests,  and 
has  emphasized  the  great  importance  of  the  employment  of  these  tests, 
to  confirm  the  nature  of  suspected  organisms  in  the  case  of  prolonged 
carriers.  He  has  in  this  way  been  able  to  release  suspected  carriers,  in 
whom  organisms  have  been  found  answering  to  the  fermentation  and 
cultural  tests  of  the  meningococcus. 

Quite  recently  he  has  investigated  the  matter  further,  making  use 
of  a  large  number  of  strains  collected  during  the  Enghsh  epidemic  of 
1915;  and  has  arrived  at  the  conclusion  that  the  difficulties  in  using 
agglutination  as  a  differential  test  were  due  to  the  fact  that  the  meningo- 
coccus is  not  a  single  species,  but  is  composed  of  a  group  of  four  separate 
organisms.  All  strains  that  he  has  collected  fall  into  one  of  the  four 
groups,  and  the  organisms  within  a  group  all  shew  constant  agglutination 
properties  sufficiently  definite  to  be  of  value  in  identification.  In  one 
instance  he  encountered  an  inagglutinable  strain  similar  to  those 
described  by  Elser  and  Hxmtoon.  It  is  at  present  an  open  question 
whether  such  groupings  of  strains  do  in  reahty  exist,  and  whether  the 
simple  serum  reactions  will  ultimately  turn  out  to  be  satisfactory,  if 
used  according  to  Gordon's  methods.  For  practical  purposes,  when 
dealing  with  a  number  of  organisms  obtained  by  the  routine  examination 
of  the  throats  of  contacts,  it  is  at  present  reasonable  to  depend  upon 
fermentation  and  cultural  characters,  to  decide  whether  a  certain  contact 
is  a  carrier  or  not ;  if  such  a  contact  remains  persistently  positive,  it  is 
then  advisable  to  go  further,  and  attempt  to  arrive  at  decision  by 
agglutinating  tests. 

The  difficulties  met  with  in  agglutination  and  other  serum  reactions 
have  given  rise  to  further  attempts  to  distinguish  separate  organisms 
which  are  similar  to  the  meningococcus,  but  yet  not  meningococci. 
Among  these  may  be  mentioned  the  pseudo-meningococcus  of  Elser 
and  Huntoon,  and  the  para-meningococcus  of  Dopter. 

The  pseudo-meningococcus  is  differentiated  by  Elser  and  Hrmtoon 
on  the  ground  that  it  fails  to  absorb  specific  agglutinins  from  a  serum 
immunized  to  the  meningococcus.    Its  other  characteristics  are  those  of 


166  Bacteriology  [CH. 

the  meningococcus.  Gordon  also  makes  use  of  a  similar  test  to  deter- 
mine the  liberation  of  prolonged  carriers,  holding  that  organisms  of 
this  type  are  not  the  cause  of  meningitis.  Elser  and  Huntoon  do  not 
state  the  source  of  their  strains.  Gordon  has  only  met  with  organisms 
of  this  type  in  cultures  from  throats.  None  of  the  many  strains  isolated 
from  cases  exhibited  this  negative  property.  It  is  therefore  probable  that 
such  a  group  of  organisms  does  exist,  indistinguishable  from  the  meningo- 
coccus culturally ;  they  are  found  in  the  naso-pharynx  but  are  not  the 
cause  of  meningitis.  At  present  it  is  reasonable  to  separate  this  group 
from  the  meningococcus  group  under  the  title  of  the  pseudo-meningo- 
coccus,  thereby  implying  its  non-pathogenic  character. 

The  para-meningococcus  was  first"  described  by  Dopter,  who  based 
its  differentiation  upon  differences  of  serum  reactions.  This  organism 
was  not  agglutinated  by  meningococcus  serum,  but  fixed  complement 
with  this.  He  not  only  found  it  in  the  naso-pharynx,  but  also 
obtained  it  from  the  meninges  and  blood  of  cases  of  meningitis. 
Dopter  and  other  observers  hold  that  cases  of  para-meningococcus 
infection  need  to  be  treated  with  a  para-meningococcus  immune  serum, 
the  meningococcus  immune  serum  being  of  no  value  in  such  cases. 
The  very  varying  agglutination  reactions  of  the  meningococcus  group 
make  it  doubtful  whether  the  para-meningococcus  is  more  than  a  rather 
extreme  variant  of  the  meningococcus.  The  matter  has  been  lately 
investigated  by  Wollstein,  who  concludes  that  the  para-meningococcus 
cannot  be  separated  into  a  strictly  definite  class,  but  should  rather  be 
considered  to  constitute  a  special  strain  among  meningococci.  The 
classification  of  the  group  of  gram-negative  diplococci,  which  have  the 
cultural  and  fermentative  characters  of  the  meningococcus,  is  at  present 
a  matter  of  difficulty  and  uncertainty.  Agglutination  reactions  are  the 
only  available  means  for  the  purpose  of  any  differentiation,  and  a  study 
of  these  reactions  shews  that  there  is  great  variabihty  among  meningo- 
coccus strains  themselves.  The  para-meningococcus  of  Dopter  is  to  be 
regarded  as  merely  a  meningococcus  with  an  extreme  variation  from 
the  commonest  type.  The  meningococcus  is  probably  not  a  single 
species,  but  consists  of  several  species  in  which  the  para-meningococcus 
is  included.  The  work  of  Gordon  indicates  that  at  least  four  species 
occur.  His  work  is  also  of  great  importance,  in  that  it  gives  reasons  for 
the  behef  that  these  four  species  have  constant  agglutinating  reactions. 
n  this  is  substantiated,  it  will  be  of  the  utmost  importance  in  the 
identification  of  carriers,  and  may  also  lead  to  such  improvements  in 
serum  treatment  as  to  place  the  value  of  this  beyond  doubt.     The 


xi]  Bacteriology  167 

existence  of  the  non-pathogeiiic  pseudo-meningococcus  group  is  almost 
certain,  its  differentiation  being  determined  by  the  absorption  test. 
The  number  of  occasions  on  which  these  organisms  are  found  in  the 
throat  is  probably  very  small,  so  that  for  practical  purposes  the 
differentiation  of  the  meningococcus  and  pseudo-meningococcus  is  not 
of  great  moment. 

Other  serological  tests  have  been  advocated  as  being  of  use  in  the 
differentiation  of  the  gram-negative  cocci,  but  no  satisfactory  results 
have  been  obtained.  Opsonic  tests  have  been  used,  but  the  phagocytic 
power  of  white  corpuscles  towards  different  strains  of  meningococci 
varies  to  a  very  great  extent.  The  opsonic  technique  is  therefore  of 
even  less  value  than  usual  for  the  purposes  of  differentiation.  For 
instance,  WoUstein  found  opsonic  methods  useless  for  differentiating 
the  meningococcus  and  gonococcus. 

Complement-fixation  tests  have  also  been  studied  to  a  considerable 
extent,  but  with  unsatisfactory  results.  Arkwright,  using  these  tests, 
arrived  at  the  conclusion  that  they  had  no  advantage  over  agglutination 
tests,  and  was  unable  to  differentiate  the  meningococcus  and  gonococcus 
by  them.  Further  researches  by  Sophian  and  Neal  confirmed  this ; 
they  also  found  that  a  differentiation  could  be  estabhshed  between 
various  strains  of  meningococci  by  such  tests.  There  is  therefore  not 
only  a  marked  affinity  between  organisms  so  different  as  the  meningo- 
coccus and  the  gonococcus  with  regard  to  these  tests,  but  also  a  great 
variation  in  the  case  of  meningococci  themselves.  They  are  therefore 
of  less  use  than  agglutination  tests  for  differential  purposes. 

Precipitin  reactions  have  been  tried  by  Dopter,  but  these  yield  even 
less  satisfactory  results. 

The  differentiation  of  the  gram-negative  cocci  is  thus  for  practical 
pm-poses  at  present  dependent  upon  the  differences  in  their  cultural 
and  fermentative  characters. 

This  chapter  may  be  concluded  by  a  short  description  of  our  routine 
method  of  deahng  with  plate  cultures  of  the  naso-pharyngeal  secretion 
of  contacts.  The  spread  plates,  having  been  incubated  for  24  hours  at 
37°  C,  are  examined  by  the  naked  eye  and  under  the  low  power  of  the 
microscope,  and  two  or  three  colonies  of  each  suspicious  group  are 
marked  with  a  grease  pencil.  Individual  colonies  are  then  picked  off 
with  a  needle,  and  two  cover-glass  preparations  made,  one  to  be  stained 
with  methylene  blue,  and  one  with  Gram  and  Bismark  brown.  It  is 
desirable  to  use  both  methods  of  staining,  as  morphological  characters 
cannot  be  adequately  studied  in  gram-stained  preparations.     Cultures 


168  Bacteriology  [ch.  xi 

are  made  of  those  colonies  which  prove  to  consist  of  gram-negative 
diplococoi.  On  the  following  day,  these  cultures  are  again  examined  to 
make  certain  that  they  are  pure.  And  the  plates  are  re-examined 
for  further  colonies  which  may  have  developed  from  the  inhibited 
meningococci.  Sub-cultures  are^  made  into  glucose,  saccharose  and 
laevulose,  and  a  culture  is  also  made  to  be  tested  in  the  incubator 
at  23°  C.  A  stock  culture  is  also  made  in  a  starch  stab  tube,  in  case 
any  tests  have  to  be  repeated.  The  sugar  tubes  are  examined  daily, 
and  are  sub-cultured  either  after  24  or  48  hours,  to  make  certain  that 
a  pure  culture  has  grown  in  them.  These  tubes  are  kept  for  a  week 
if  no  definite  reaction  has  taken  place.  The  very  definite  alkaUne 
reaction  of  M.  catarrhaHs  and,  to  a  less  degree,  of  the  meningococcus, 
is  useful  in  shewing  that  a  satisfactory  test  has  been  made.  The  culture 
in  the  23°  C.  incubator  is  kept  at  this  temperature  for  two  to  three 
days ;  if  at  the  end  of  this  period  there  is  still  little  or  no  sign  of  growth, 
the  tube  is  placed  in  the  37°  C.  incubator.  The  test  is  only  considered 
satisfactory  if  a  strong  growth  is  then  obtained ;  if  this  does  not  occur, 
the  test  is  repeated.  We  have  found  that  on  the  whole  these  methods 
are  satisfactory,  but  do  not  beheve  that  a  single  step  can  be  safely 
left  out.  If  sufficient  precautions  are  taken  to  sub-culture  thickly, 
and  the  proper  media  are  used,  an  organism  seldom  fails  to  grow  in 
the  sugar  tubes,  and  the  cold  incubator  test  also  seldom  fails.  We  do 
not  consider  advisable  the  shortening  of  these  tests,  either  by  the  use 
of  plates  containing  glucose  and  an  indicator,  such  as  Htmus,  when 
sowing  from  the  original  swab,  or  by  the  use  of  solid  media  containing 
sugar  and  indicator  for  testing  fermentation  reactions  in  sub-culture. 
The  differentiation  of  the  pseudo-meningococcus  from  the  meningo- 
coccus can,  by  definition,  only  be  made  by  serum  reactions,  and  the 
only  reliable  method  consists  in  making  use  of  absorption  tests.  The 
length  of  time  necessary  for  performing  such  tests  renders  them  of 
practical  value  only  in  the  case  of  prolonged  carriers.  The  numbers  of 
pseudo-meningococcus  carriers  met  with  are  usually  small.  No  great 
administrative  error  is  thus  committed  in  treating  them  as  if  they 
were  meningococcus  carriers,  if  they  are  only  temporarily  carriers  of  the 
pseudo-meningococcus. 


PLATES 


PLATE   I 

A  drawing  representing  the  Macular  Rash,  sketched  on  the  fourth  day,  from 
a  case  which  recovered.  The  extensor  surface  of  the  forearm  and  dorsum  of  the 
hand  are  hero  shewn,  as  representing  one  of  the  most  favoured  sites  of  the  eruption. 
The  individual  maculae  are  seen  to  vary  in  size,  a  variation  whose  actual  limits 
range  from  that  of  a  millet  seed  to  a  No.  1  shot.  The  colour  of  the  eruption 
may  be  seen  to  vary  from  that  of  a  scarlet  geranium  to  the  hue  of  a  ripe  grape. 
Some  of  the  larger  maculae  present  a  deep  purple  centre  surrounded  by  a 
reddish  peripheral  zone.  The  appearance  of  the  knuckles  illustrates  the  larger 
size  assumed  by  the  rash  at  points  exposed  to  pressure  or  injury.  The  maculae  in 
these  situations  become  larger  in  size,  more  irregular  in  shape  and  of  a  deeper  purple 
colour.  In  some  instances  the  cutis  may  be  shghtly  raised.  The  variation  in  size 
and  colour  of  the  maculae  is  present  from  their  first  appearance,  and  does  not  indicate 
their  outbreak  in  successive  crops.  At  the  end  of  two  days  the  rash  begins  to  fade, 
leaving  behind  it  spots  of  livid  staining  of  a  slaty  blue  colour. 


Plate  I 


*    ♦ 


/  /  ^ 


PLATE   II 

Kg.  1.  A  drawing  representing  the  Erythematous  Rash  sketched  on  the 
thirteenth  day,  from  a  hydrocephalic  case  which  subsequently  died.  The  appear- 
ance represented  is  that  seen  on  the  abdominal  wall;  the  mottled  appearance  is 
characteristic.  The  rash  is  essentially  evanescent,  often  only  lasting  a  few  hours, 
the  colour  naturally  varies  at  different  stages.  The  different  "lines  "  which  may  be 
observed  range  from  pink,  as  shewn  in  this  drawing,  to  bluish  red.  As  the  eruption 
fades  shght  staining  may  be  left  behind. 

The  rash  more  frequently  occurs  on  the  trunk  than  on  the  extremities. 

Kg.  2.  A  drawing  taken  shortly  after  death  representing  the  Petechial  Rash, 
from  a  fulminating  case,  which  died  in  thirty-six  hours.  The  picture  shews  the 
appearance  presented  by  the  rash  in  the  skin  overlying  the  great  trochanter.  The 
comparatively  large  size  of  the  petechiae  and  their  brOhant  copper  colour,  persistent 
after  death,  and  contrasting  with  the  surrounding  skin,  well  illustrates  the  tendency 
of  the  rash  to  assume  its  more  marked  form  over  points  of  pressure. 


Plate  II 


PLATE   III 

A  drawing  representing  another  aspect  of  the  Petechial  Bash,  taken  from  a 
patient  who  died  on  the  fom-th  day.  Here  again  the  position  of  the  rash  over  points 
of  pressure  is  exemphfied,  and  its  essentially  traumatic  character  indicated  by  the 
bruise  underlying  the  eruption.  In  contrast  with  the  last  plate,  the  smaller  size 
and  more  vivid  scarlet  colour  of  the  individual  petechiae  is  noticeable.  At  one 
spot  the  petechiae  have  coalesced,  their  fusion  giving  rise  to  a  haemorrhagic  blotch 
of  considerable  size. 


Plate  III 


'  •""■'t''.-' 


^m. 


PLATE   IV 

A  drawing  representing  the  Purpuric  Rash,  taken  from  a  fulminating  case  -which 
died  in  under  thirty-six  hours  from  onset.  As  will  be  seen  from  the  picture,  the 
blotches  vary  markedly  in  size,  some  being  no  larger  than  the  petechiae  shewn  in 
the  preceding  plates.  One  haemorrhagic  spot  or  vibex  is  of  large  size,  and  several 
others  of  equal  magnitude  were  scattered  over  the  body.  In  this  case  vibices  of 
considerable  size  occurred  on  the  face.  The  uniformly  dark  purple  colour  of  the 
blotches  affords  a  marked  contrast  to  the  tints  depicted  in  the  former  plates. 


Plate  IV 


PLATE  V 

Fig.  1.  From  Andre.  The  comiections  of  the  sub-arachnoid  space  and  the 
upper  regions  of  the  nose  in  man.  Drawn  from  an  injection  into  the  sub-arachnoid 
space  in  an  infant.  The  outer  wall  of  the  nasal  cavity  is  shewn.  The  channels 
injected  all  lie  above  the  level  of  the  superior  turbinate  bone,  with  the  exception  of 
some  which  pass  down  the  posterior  wall  of  the  naso-pharynx  for  a  considerable 
distance.  This  region  corresponds  remarkably  with  the  site  of  infection  by  the 
meningococcus. 

Fig.  2.    A  photograph  illustrating  Head  Retraction,  taken  on  the  third  day,  in  a 

case  which  was  completely  convalescent  in  eleven  days.     The  photograph  was  taken 

from  above,  and  shews  the  position  which  the  head  assumes  in  relation  to  the  vertebral 

column.     The  occiput  comes  to  he  in  hne  with  the  shoulders,  the  chin  is  tilted 

■  upwards  and  the  trachea  is  very  prominent,  the  skin  over  it  being  tightly  stretched. 


Plate   V 


12—2 


PLATE  VI 

Two  photographs  illustrating  Kernig's  Sign.  The  sign  is  well  marked  in  Fig.  1, 
absent  in  Fig.  2.  In  Fig.  1  the  spasm  of  the  hamstring  muscles  prevents  extension- 
of  the  leg  on  the  thigh  beyond  a  right  angle.  This  spasm  is  clearly  demonstrated 
by  the  obviously  tense  condition  of  the  hamstring  tendons.  In  Fig.  2,  on  the  con- 
trary, which  was  taken  from  a  normal  person,  complete  extension  has  been  obtained. 


Plate   VI 


PLATE  VII 

The  brain  of  an  acute  fatal  case,  drawn  a  few  hoiu's  after  death;  the  patient 
died  on  the  fifth  day  of  illness.  Viewed  from  the  vertical  aspect.  The  whole 
cortex  of  tlie  brain  is  intensely  congested,  so  that  the  surface  appears  bright  red  in 
colour:  the  darker  veins  stand  out  conspicuously.  Purulent  infiltration  is  widely 
scattered  over  the  siu'face,  the  pus  being  distributed  especially  around  the  larger 
vessels,  which  in  places  are  obsciu'ed  by  it.  One  particularly  large  aggregation  is 
present  over  the  motor  area  on  the  left  side.  A  right  hemiplegia  was  present  in  this 
case,  which  can  be  held  to  have  been  caused  by  the  purulent  deposit  over  the  motor 
area.    The  cord  of  this  case  is  shewn  on  Plate  X,  fig.  1. 


Plate  VII 


PLATE  VIII 

The  brain  of  a  suppurative  case,  viewed  from  the  basal  side ;  the  patient  died  on 
the  nineteenth  day  of  illness. 

The  base  of  the  brain  is  completely  covered  with  a  thick  adherent  purulent  mass, 
which  obscures  all  the  structures  from  the  optic  chiasma  to  the  cerebellum,  and 
extends  laterally  to  the  temporo-sphenoidal  lobes.  The  circle  of  Willis  is  completely 
obhterated,  only  the  cut  ends  of  the  internal  carotid  arteries  can  be  seen.  The 
paired  cerebral  nerves  are  shewn  emerging  from  the  purulent  mass.  The  pus  extends 
over  the  pons  and  medulla  and  completely  clothes  the  region  of  the  cisterna  magna, 
it  also  covers  the  cerebellum  on  either  side  of  this  to  some  considerable  extent. 
The  cerebrum  itself  is  practically  free  from  pus  and  its  vessels  are  not  congested. 


Plate    VIII 


PLATE   IX 

Fig.  1.  The  brain  of  a  chronic  case  with  hych'ocephalus,  which  died  on  the  fifty- 
first  day  of  ilbiess.  The  specimen  was  hardened  whole  and  opened  by  a  median 
incision  some  weeks  later.  All  the  ventricles  of  the  brain  are  dilated.  The  fourth 
ventricle,  IV,  is  especiaUy  enlarged  and  its  floor  is  furrowed  owing  to  the  pressure 
of  the  fluid  which  it  contained.  The  iter  is  not  greatly  distended,  but  the  thii-d 
ventricle,  III,  is  greatly  enlarged.  The  foramen  of  Mimro,  M,  forming  its  connection 
with  the  lateral  ventricle  L,  is  very  conspicuous.  The  lateral  ventricles,  L,  were 
also  so  greatly  enlarged  as  to  allow  of  the  complete  insertion  of  the  forefinger.  The 
convolutions  of  the  brain  are  flattened,  but  not  to  an  extreme  degree. 

The  cord  of  the  same  case  is  shewn  in  Plate  X,  fig.  .3.  The  block  in  the  sub- 
arachnoid space  in  the  upper  dorsal  region  prevented  the  rehef  of  ventricular  pressure 
by  lumbar  puncture.  There  was  no  obvious  block  in  the  region  of  the  choroid  plexus 
of  the  foiu-th  ventricle,  though  this  was  adherent  to  a  considerable  degree  to  the 
cerebellum. 

Fig.  2.  The  brain  of  an  acute  case  which  died  on  the  tenth  day  of  iUness  from 
a  retroperitoneal  haemorrhage.  Even  at  this  early  stage  well  marked  hydro- 
cephalus is  present,  all  the  ventricles  of  the  brain  being  very  distended ;  the  iter 
between  the  third  and  fourth  ventricle  is  also  dilated. 

Drawn  from  the  fresh  specimen  24  hours  after  death.  A  complete  occlusion 
of  the  drainage  channels  of  the  roof  of  the  fom-th  ventricle  caiuiot  have  existed, 
as  nearly  two  ounces  (50  c.c.)  of  cerebro-spinal  fluid  were  removed  by  lumbar 
puncture  the  day  before  death. 


Plate  IX 


PLATE  X 

Pig.  1.  The  cord  of  an  acute  fatal  case;  the  patient  died  on  the  fifth  day  of 
iUness.  The  brain  of  this  case  is  shewn  in  Plate  VII.  In  correspondence  with  the 
brain  there  is  great  congestion  throughout  the  cord,  which  is  especially  intense  in  the 
lumbar  region  at  C.  Little  pus  was  present,  a  collection  is  to  be  seen  at  A,  and 
another  at  B,  which  forms  a  ring  round  the  cord  in  this  region.  The  latter  might 
later  have  given  rise  to  obhteration  of  the  sub-arachnoid  space  at  this  spot. 

Fig.  2,  The  cord  of  a  suppurative  case ;  the  patient  died  on  the  twenty-second 
day  of  illness.  The  lower  two-thirds  of  the  cord  are  completely  coated  with  a  dense 
adherent  mass  of  inspissated  pus.  The  upper  thii-d  also  is  partially  coated-  some  of 
the  pus  in  this  region  became  detached  during  preparation  of  the  specimen  and  is 
not  shewn.     There  is  little  congestion  of  vessels  present. 

Fig.  3.  The  cord  of  a  case  which  died  with  hydrocephalus  on  the  fifty-first  day 
of  disease.  The  brain  of  this  case  is  shewn  in  Plate  IX,  fig.  1.  The  cord  and 
theca  are  seen  to  be  adherent  at  various  places.  This  adherence  is  complete  in  the 
upper  dorsal  region,  so  that  the  theca  could  not  be  stripped  from  the  cord  on  any 
aspect  When  the  cord  was  held  up,  directly  after  removal  before  the  theca  was 
opened,  the  latter  bulged  above  the  point  of  adherence  but  was  empty  below, 
shewing  that  the  adherence  was  complete.  No  pus  was  present  either  on  the 
brain  or  the  cord.     The  cord  was  not  congested. 

Pig.  4.  The  cord  of  a  case  with  a  temporo-sphenoidal  abscess,  which  spread  to 
the  base  of  the  brain  and  thence  down  the  cord.  The  cord  is  coated  with  pus  over 
a  considerable  part  of  its  length,  and  the  condition  might  well  have  been  due  to 
the  meningococcus.  Clinically  the  case  was  identical  with  a  case  of  cerebi-o-spinal 
fever.  The  infectmg  agents  were  a  gram-positive  diplococcus  and  a  fusiform 
bacillus,  neither  of  which  could  be  cultivated. 


Plate  X 


"^"l 


/; 


*r 


Z 


l:X0 


Fig.  1 


PLATE   XI 

Pig.  1.  Section  of  the  meninges  in  an  acute  fatal  case  shewing  the  chief  site  of 
the  meningococcal  infection.  The  tissue  was  embedded  in  gelatine,  cut  frozen,  and 
stained  with  Bismark  brown. 

In  the  lower  part  of  the  picture  the  outer  layers  of  the  wall  of  a  large  blood- 
vessel are  represented,  above  this  two  perivascular  spaces,  and  above  that  the 
tissues  of  the  sub-arachnoid  space  infiltrated  with  exudate.  A  thin  strand  of  tissue 
separates  the  two  spaces,  and  in  the  wall  of  tins  numerous  pans  of  cocci  are  seen 
to  be  embedded.  These  spaces  are  Hned  by  endothehal  cells  with  long  nuclei.  The 
exudate  consists  mainly  of  polymorphonuclear  cells  with  deeply  staining  nuclei, 
but  a  considerable  number  of  mononuclear  cells  with  a  ia.ir  amount  of  protoplasm 
are  also  present,  whose  nuclei  stain  less  deeply.  A  small  lymphocyte  and  a  red  cell 
are  seen  in  the  space  in  the  upper  right  hand  corner  of  the  picture.  A  pale  zone  is 
present  round  the  pairs  of  cocci,  which  resembles  a  capsule. 

Fig.  2.  A  film  of  the  cerebro-spmal  fluid  from  a  fulminatmg  case.  The  pus 
was  allowed  to  coUeot  at  the  bottom  of  the  coUeoting  tube,  by  keeping  the  latter 
upright  for  a  short  time.  Drawn  from  a  fresh  film  stamed  with  methylene  blue, 
and  mounted  in  water. 

Polymorphonuclear  cells  predominate,  though  a  number  of  lymphocytes  of 
various  kinds  are  also  present.  The  meningococci  are  mainly  within  the  bodies 
of  leucocytes,  being  often  present  in  great  numbers  in  one  particular  cell.  A  few 
extraoeUular  cocci  are  also  seen.  The  cocci  lie  in  pau-s,  the  individuals  of  which  are 
often  flattened;  occasionally  four  cocci  form  a  tetrad.  The  individual  pau-s  vary 
in  depth  of  stain;  some  have  a  distinctly  paler  zone  round  them,  which  resembles 
a  capsule. 


Plate  XI 


,W 


%._  r^  ♦  :^ 


H^ 


•  »••- 


• 


^ 


Kg.  2 


APPENDIX  I 

While  this  book  was  in  the  press,  a  remarkable  examj^le  of  the 
spread  of  the  meniugococcus  from  carrier  to  carrier  occurred  in  our 
district.  A  certain  regiment  was  transferred  from  a  station  in  the 
South  of  England  on  December  31st.  A  few  days  after  its  arrival 
notice  was  sent  that  a  man,  B,  belonging  to  the  regiment,  who  had  been 
left  behind  sick,  had  died  of  cerebro-spinal  fever.  This  man  had  slept 
with  eighty  others  in  a  large  hut.  The  eighty  men  were  swabbed  on 
January  6th,  that  is  to  say,  somewhat  over  a  week  after  the  removal 
of  the  man  B  from  among  them,  and  six  days  after  their  arrival  in  their 
new  billets.  A  surprisingly  high  percentage  of  carriers  was  found  at 
this  examination,  no  less  than  twelve  men  giving  positive  results,  the 
percentage  therefore  being  15. 

An  examination  of  their  billets  shewed  that  these  carriers  could  be 
looked  upon  as  forming  two  distinct  foci  of  infection;  out  of  twenty 
small  rooms  which  were  needed  to  billet  the  eighty  men,  only  eight  con- 
tained carriers.  The  larger  group  of  affected  rooms  consisted  of  six  which 
are  shewn  in  Plans  I  and  II.  Plan  II  represents  the  floor  directly  above 
Plan  I  in  the  same  building.  A  second  focus  consisted  of  two  rooms  in 
another  building;  the  rooms  were  next  to  one  another  on  the  same 
floor  and  are  shewn  in  Plan  III;  the  remaining  man  is  not  shewn  on 
the  plan  as  he  developed  mumps  on  the  day  of  arrival  and  was  therefore 
isolated  at  once.  The  carriers  found  at  the  first  examination  are 
marked  in  Plans  I,  II  and  III  by  a  black  cross.  As  this  distribution 
was  so  striking,  when  these  carriers  were  removed  from  the  billets  ori 
January  13th,  a  re-examination  of  the  remaining  men  in  these  rooms 
was  made.  The  men  in  rooms  6  of  Plan  I,  and  1  of  Plan  II,  were 
included,  as  these  rooms  could  only  be  reached  by  passing  through  a 
room  in  which  a  carrier  had  been  found.  At  this  second  examination 
five  more  carriers  were  discovered;  these  men  had  all  been  negative 
at  the  examination  on  January  6th.  The  deduction  may  therefore  be 
made  that  they  were  infected  by  certain  of  the  original  carriers  between 
January  6th  and  January  13th.     These  carriers,  discovered  at  the  second 


Plan  I 


+000 

^_ 

1       6 

00 

\. 

Plan  II 


Plan  III 


+      Positive  1st  Examination. 
"^      Positive  2nd  Examination. 


O     Negative  Ist  and  2nd  Examinations. 

®  Negative  1st  and  2nd ;  Positive  3rd. 
Carrier  of  infection  to 
new  billet. 


Appendix  I  193 

examination  on  January  ISth,  are  shewn  in  Plans  I,  II  and  III  by  a  cross 
in  outline.  The  remaining  seventeen  men  in  the  infected  rooms  gave 
negative  results ;  they  had  thus  been  twice  negative,  on  Jgjiuary  6th  and 
on  January  13th.  The  study  of  Plans  I,  II  and  III  shews  that  three 
rooms  were  chiefly  affected  in  the  larger  focus,  namely  rooms  1,  2  and 
3  of  Plan  I.  Not  only  were  six  out  of  the  nine  original  carriers  in  this 
focus,  billeted  in  these  three  rooms,  but  also  the  three  freshly  infected 
carriers  of  the  focus,  found  positive  at  the  second  examination,  were 
billeted  here.  The  remaining  rooms,  4  and  5  of  Plan  I  and  2  of  Plan  II, 
each  contained  only  one  original  carrier,  and  no  spread  of  infection  had 
taken  place  in  them.  In  the  second  focus  one  original  carrier  was 
found  in  each  of  the  rooms  3  and  4  of  Plan  III.  Each  of  these  carriers 
had  infected  one  other  man  before  the  second  examination  on  January 
13th 

In  order  to  try  to  prevent  any  further  spread  of  infection,  four  of 
the  five  men,  who  ultimately  proved  positive  at  the  second  examination, 
were  removed  on  January  15th  to  isolation,  the  appearance  of  their 
plate  colonies  being  considered  sufficient  justification  for  this  course. 
The  remaining  eighteen  men  were  transferred  to  fresh  billets,  the  arrange- 
ment of  which  is  shewn  in  Plan  IV.  Further  investigation  of  the  plates 
of  the  second  examination  shewed  that  a  fifth  man,  one  of  the  eighteen 
transferred  to  the  new  billets,  was  also  positive.  A  third  examination 
of  the  eighteen  men  was  therefore  made  on  January  19th.  The  next 
day  the  plates  were  examined  and  seven  men,  inclusive  of  the  man  found 
positive  at  the  second  examination,  were  suspicious.  These  seven  were 
immediately  removed  to  isolation  and  the  remaining  eleven  were 
re-examined  on  the  next  day,  January  21st.  On  this  occasion  these 
eleven  were  again  negative,  this  being  their  fourth  examination.  As  it 
was  considered  that  further  infection  had  been  stopped,  they  were 
released  and  not  further  examined. 

Plan  IV  shews  that  in  room  1  the  man  who  was  erroneously  allowed 
to  escape  isolation  had  infected  one  other  man.  The  man  positive  on 
the  second  examination  is  shewn  by  a  cross  in  outline,  and  the  man 
positive  on  the  third  examination  by  a  black  cross.  In  room  2  one  man 
was  found  positive  on  the  third  examination,  he  had  been  in  room  2  of 
Plan  I  previous  to  removal  and  is  shewn  in  both  plans  by  a  cross 
with  a  circle  round  it.  He  was  there  in  contact  with  carriers  for 
two  days,  from  January  13th  to  15th,  after  his  second  examination 
which  had  proved  negative.  It  can  be  presumed  that  he  was  infected 
in  the  original  billet  during  this  time.     In  rooms  3  and  4  of  Plan  IV 

F.  &  G.  13 


194 


Appendix  1 


four  fresh  carriers  were  found,  three  in  room  4  and  one  in  room  3. 
One  of  the  men  in  room  4,  LD,  had  come  from  room  1  of  Plan  I ;  the 
other  three  had  come  from  rooms  2  of  Plan  II,  and  5  of  Plan  I,  both  of 
which  had  been  completely  negative  at  the  second  examination.  We 
may  therefore  assume  that  the  man  LD  had  brought  the  infection  from 
room  1  of  Plan  I  and  had  infected  the  other  three,  he  himself  having  been 
infected  between  the  13th  and  15th.  The  two  men,  who  were  negative 
at  the  second  examination  but  can  be  considered  to  have  brought  the 
infection  to  the  new  billets,  are  shewn  in  both  Plans  I  and  IV  by  a  black 
cross  with  a  circle  round  it.  The  general  plan  of  the  spread  of  infection 
is  shewn  in  Plan  V;  the  figures  following  the  abbreviated  names  refer 

Plan  IV 


■fr      Positive  2nd  Examination,  but  removed  to  new  billet. 

®      Negative  1st  and  2nd  Examinations;  Positive  3rd.     Carrier 
of  infection  to  new  biUet. 

+      Positive  3rd  Examination,  infected  in  new  billet. 

O     Negative  all  four  Examinations. 


to  the  charts  I  to  IV,  and  shew  the  rooms  in  which  the  various  men 
became  infected.  The  most  extensive  spread  is  seen  to  have  passed 
through  five  generations,  namely  B,  SR,  LS,  LD,  and  finally  BD,  BN, 
and  BU.  This  extensive  spread  took  place  between  about  December 
28th  and  January  19th,  a  period  of  approximately  three  weeks;  it  is 
therefore  clear  that  under  suitable  circumstances  a  wide  dissemination 
of  the  meningococcus  from  carrier  to  carrier  may  take  place  very 
quickly.  Another  part  of  the  table  is  of  interest,  the  series  in  which 
BS  was  the  early  carrier.  This  man  was  originally  billeted  with  CE 
in  room  3  Plan  I.  At  the  time  of  the  first  examination  he  had  been 
removed  to  hospital  on  account  of  a  slight  rise  of  temperature,  and 


Appetidix  I 


195 


another  man  ES  had  taken  his  place  in  room  3.  BS  was  examined 
while  in  hospital  and  was  fomid  to  be  positive.  The  plates  of  the  other 
two  men,  taken  on  January  6th,  were  unsatisfactory,  only  a  very  few 
streptococci  being  grown ;  they  were  therefore  re-examined  on  January 
8th  when  both  grew  the  meningococcus  in  quantity  and  in  almost  pure 
culture.  BS  was  removed  on  January  5th.  It  is  probable  that  meningo- 
cocci were  not  present  in  quantity  in  the  throats  of  CE  and  ES  on 
January  6th  and  that  they  had  only  been  recently  infected.  The  path 
of  infection  would  then  be  that  of  Plan  V.     CE  would  have  been  infected 

Plan  V 
B 


I  \  \  \  1  I  I  I  I 

GN.ll,2   BE.1,0   BG.I.i   BS.I,3    CT.1.2  CH.l,2    SR.I,l    ilfS.111,3    Br.III,4 


I  ! 

CE.I,3    ML    Bi.1.2    FBi.1,2    LS.I,1    SE.III,3     FR^.IIhi 

&IV,1 


E8I,3 


I     1-2 
MB.IV,2  LZ).I,1&IV,4        OS.IV.l 


5jD.IV,4 


I  I 

BN.TV,i    BV.IV,3 


This  shews  the  probable  path  of  infection.  The  letters  indicate  the  name  of  the 
carrier,  the  roman  numbers  the  plan,  and  the  arable  numbers  the  room  on  the  plan  in 
which  the  particular  carrier  was  billeted. 

by  BS  before  his  removal  to  hospital  and  ES  in  turn  by  CE.  While 
the  first  examination  was  being  carried  out,  BS  was  released  from 
hospital  and  was  billeted  with  ML.  At  the  second  examination  ML 
was  found  to  be  positive,  though  he  had  been  one  of  the  original  eighty 
and  had  been  negative  at  the  first  examination. 

The  interest  of  these  observations  lies  in  the  fact  that  the  men, 
who  proved  positive  at  the  2nd  and  3rd  examinations,  had  all  been 
examined  either  once  or  twice  previously  with  negative  results;  there 
is  therefore  some  considerable  justification  for  assuming  that  the  spread 
of  infection  followed  the  path  described  here. 


13—3 


APPENDIX   II 

FORMULA  FOB  PEA  EXTRACT  TRYPSIN  AGAR   (GORDON) 

1.  Take  50  grammes  of  pea  flour  (ordinary  Pearce  Duff's)  and  add 
to  1  litre  of  distilled  water  with  100  grammes  of  salt.  Mix  and  steam 
for  half  an  hour,  stirring  occasionally,  allow  to  settle,  and  filter,  then 
sterilize  and  label  "Saline  Pea  Extract."  This  pea  extract  should 
preferably  be  freshly  made  for  each  batch  of  agar. 

2.  Take  some  fresh  bullocks'  hearts,  free  from  fat  and  vessels, 
mince  the  meat  very  finely  and  weigh.  To  each  ^  kilo  add  1  litre  of 
water  and  make  faintly  alkaline  to  litmus  with  20  per  cent.  KOH 
solution.  Heat  this  slowly  to  75°-80°  C.  for  5  minutes.  Cool  to  37°  C. 
and  add  1  per  cent,  of  liquor  trypsinae  Co  (Allen  and  Hanbury)  and 
keep  it  at  37°  for  2|  to  3  hours.  When  trypsinizing  is  finished  test  for 
peptone  with  copper  sulphate  and  KOH  as  below,  then  render  slightly 
acid  with  glacial  acetic  acid  and  bring  slowly  to  the  boil  for  a  quarter 
of  an  hour.  Leave  over  night  in  a  cool  place  and  syphon  off  the  clear 
liquid  in  the  morning.  Make  faintly  alkaline  to  litmus  and  sterilize  in 
the  autoclave  at  118°  C.  for  1  hour  on  each  of  two  days  (if  not  to  be 
used  at  once). 

To   make   Trypsin   Broth   Pea   Extract   {Legumin)   Agar.     Take   a 

measured  quantity  of  the  trypsinized  broth,  add  2  per  cent,  of  agar 

fibre  (see  below  for  preparation)  and  -215  grammes  of  calcium  chloride 

per  litre.     Autoclave  at  118°  C.  for  three-quarters  of  an  hour  to  dissolve 

N 
the  agar.     Mix  together  in  an  urn  or  saucepan ;   titrate  with  ^-^  KOH 

while  boiling,  using  phenol  phthalein  as  the  indicator,  and  add  the 
necessary  amount  of  normal  KOH  to  give  an  absolutely  neutral  reaction. 
Cool  to  60°  C,  add  white  of  egg  (two  to  a  litre)  beaten  up  with  the 
crushed  shells,  autoclave  again  at  118°  C.  for  75  minutes  (or  in  the 
steamer  for  2  hours).  Filter,  add  to  the  filtrate  5  per  cent,  of  the 
sterile  pea  extract  and  sterilize  in  the  ordinary  way. 


Appendix  II  197 

Preparation  of  Fibre  Agar.  Weigh  out  the  required  quantity,  cut 
up  small  with  scissors,  place  in  a  large  flask  or  enamel  pail  and  wash 
twice  quickly  in  water.  Drain  thoroughly;  add  water  just  to  cover, 
and  put  in  glacial  acetic  acid,  2-5  c.c.  per  litre  of  water.  Mix  thoroughly 
and  leave  for  a  quarter  of  an  hour.  Pour  off  the  liquid  and  wash 
thoroughly  four  or  five  times  to  make  sure  that  all  the  acetic  acid  is 
washed  out.     Drain  carefully  and  use  as  above. 

Biuret  Reaction  for  Peptone.  Take  5  c.c.  of  broth,  add  -1  c.c.  of 
5  per  cent,  solution  of  CUSO4.  Mix,  and  then  add  5  c.c.  normal  KOH. 
A  true  pink  colour  indicates  that  trypsinization  is  sufficient;  a  bluish 
purple  shade,  that  it  is  incomplete. 


BIBLIOGRAPHY   AND  INDEX   OF  AUTHORS 

The  various  pages  in  this  book-,  on  which  an  author  is  quoted,  will  be  found  in  the  last 
column;  the  subject  matter  of  the  particular  quotation  uull  be  found  in  the  second 
and  third  columns  opposite  the  page  number. 


Autlioi- 

Title  of  Refei-ence 

Page  in 
Refcr- 

P.ige 

ADAMI,  J.  G.  Lt.  Col.      . 

Personal  Communication  . 

54 

ALBRECHT,        H.        and 

GHON,  A.         .        .        . 

"Ueber    die    Aetiologie    und    patho- 
logisclie  Anatomie  der  Meningitis 
Cerebrospinalis  Epidemica" 
Wien.  KHn.  Wocli.     No.  41.     1901 

98 

118, 152, 
162 

154, 

andr:^,  J.  M.  . 

"Contribution   a  I'lStude  des  Lym- 

phatiques  du  Nez" 
Thfese    de    Paris.     1905.     G.    Stein- 

theU.     Paris 

94 

ANDREWES,  F.  W.  . 

"A    Case    of    Acute    Meningococcal 

43,  97,  117 

Septicaemia"       .... 

Lancet.     Vol.  I.     1906 

1172 

AIRALDI     .... 

Quoted    by    Corradi,    Annali     delle 
Epidemiche     occorse     in     Italia. 
Vol.  vn.     Appendice  . 

963 

4 

ARKWRIGHT,  J.  A. . 

"On    the    occurrence  of    the  Micro- 
coccus Catarrhahs  in  normal  and 
catarrhal  noses  and  its  differentia- 
tion   from    other    gram-negative 
Cocci" 

.Journal  of  Hygiene.     Vol.  vn.     1907 

"Discussion    on  Epidemic  Cerebro- 
spmal  Meningitis" 

Proc.    Roy.    Soc.    Med.      Vol.   vm. 
No.  5.     1915 

145 
69 

167 
3 

BARKER,  A.  E.  J.    . 

"  The  possible  uses  of  lumbar  puncture 
in  the  treatment  of  Otitic  Menin- 
gitis"   

Proc.  Roy.  Soc.  Med.     Vol.  i.     Sur- 
gical Section.     March,  1908 

393 

31 

BATTEN,  F.  E.  . 

"Meningitis" 

AUbutt  and  RoUeston's  System   of 
Medicine.     Vol.  vin.     1910 

165 

60,61 

BETTENCOURT     A.     and 

FRANCA,  C.     .         .         . 

"De    la   Meningite    Cerebro-Spinale 
epidemique   et   son   agent   speci- 
fique" 

Bulletin  de  Flnstitut  Pasteur.   Tome 
n.     1904 

338 

162 

BIOT 

]5tude    Clinique    sur   la   Respiration 
Cheyne  Stokes.     Paris.     1878 

18,45 

Bibliography  and  Index  of  Authors 


199 


Title  of  Reference 


BOLDUAN,  C.  AND  CtOOD- 
WIN,  M.  E.      .         .        . 


BROWN,  F.  J. 


BEUNS  AND  HOHN  . 
BURTON  FANNING,  Major 
F.  W 


CARR,  J.  W.   . 
CHALMERS,  A.  K.  . 

CONNER,  L.  A 

CONNER  AND   STILLMAN 

CORNING,  L.      .        .        . 


COUNCILMAN,  MALLORY 
AND  WRIGHT 


CROHN,  B. 


CURRIE,  J.  E.  AND  MAC- 
GREGOR,  A.  S.  M. 


DOPTER,  G. 


DUNHAM,  E.  K. 


"A  Clinical  and  Bacteriological  Study 
of  the  communicabillty  of  Cerebro- 
spinal Meningitis  and  its  pro 
bable  source  of  contagion"  . 

Medical  News.     Vol.  Lxxxvn.     1905 

"On  an  epidemic  of  Cerebro-spinal 
Meningitis  at  Rochester  with  intro 
ductory  remarks  on  other  epidemics 
that  preceded  it" . 

Trans.  Epidem.  Soc.  Vol.  ii.  Part  ii. 
Session  1865-66 

Khn.  Jahrbuch.     x\Tn.     1908 . 


Personal  Communication  . 


Basic 


"Non-Tuberculous    Posterior 

Meningitis  in  Infants" 
Medico-Chir.  Trans.    Vol.  Lxxx.  1897 
"Discussion    on    Epidemic    Cerebro 

Spinal  Meningitis" 
Proc.    Roy.    Boc.    Med.     Vol.    vni, 

No.  5.     Sect  of  Epidem.     1915 
"Biot's  Breathing"  . 
Amer.    Jour,    of    Medical    Sciences, 

cxu.     1911 
"  A  Pneumograpliic  Study  of  respira 

tory  irregularities  in  Meningitis" 
Archives  of  Internal  Medicine.  IX.  1915 
"  Spinal  Anaesthesia  and  Local  Medi' 

cation  of  the  cord" 
New  York  MedicalJoumal.  xur.  1885 

Report  of  State  Board  of  Health, 
Massachusetts.     Boston.     1898     . 

"An  improved  apparatus  for  esti- 
mating the  pressure  in  the  Cerebro- 
spinal System"    .         .        .         . 

Journal  of  the  American  Medical 
Association.     Vol.  Lvi.     1911 

"The  Serum  Treatment  of  Cerebro- 
spinal Fever  in  the  City  of  Glasgow 
Fever    Hospital,    Belvidere,     be- 
tween May  1906  and  May  1908" 
Lancet.     Vol.  n.     1908 

"fitude  de  quelques  germes  isoles  du 
Rhinopharynx  voisin  du  Meningo- 
cocques  Para-meningococques"    . 

Compt.  Rend,  de  Soc.  de  Biol.  Lxvn. 
1909 

"Comparative  Studies  of  Diplococci 
decolourized  by  Gram  Method 
obtained  from  the  Spinal  fluid 
and  the  Nares  in  cases  of  Cerebro- 
spinal Fever"        .         .         .         . 

Joum.  Infect.  Dis.  Sup.  n.  Feb. 
1906 


391 

285 


50 
350 
203 

483 


9,  119,  148, 

153 

34 


10,  106 


107, 165, 166, 
167 


200 


Bihliography  and  Index  of  Authors 


Page  in 

Author 

Title  of  Reference 

Refer- 

Page 

DUNN         .... 

Boston  Medical  and  Surgical  Journal. 

73 

u.     1908 

370 

ELSER.  W.  J.  AXD  HUN- 

TOON,  F.  M.  . 

''Studies  in  Meniagitis"     . 

519 

105,  117 

Journal  of  Medicaf Research.  Vol.  xx. 

384 

147 

1909 

493 

152 

494 

153 

418 

158 

433 

160,  163 

384 

164. 165, 166 

EMBLETON.        D.       akd 

PETERS,  E.  A.       . 

"C'erebro -spinal     Fever      and      the 

il04 

Sphenoidal  Sinus" 

Lancet.     Vol.  i.     1915 

1078 

PERRON,  M.      . 

"La  Meningite  Cerebro-Spinale  Epi- 

demique  dams  les  Landes,  1837-39  " 

Bulletin  Medical.     Paris.     VoL  yxtt. 

4 

1910 

3 

FLEXNER,  S.     .        .        . 

"The  results  of  serum  treatment  ill 

9.  65.  66,  71, 

1300   cases  of   Epidemic  Menin- 

74, 75.  76, 87, 

gitis"    

153 

Journal   of  Experimental  Medicine. 

xvn.     1913 

553 

"Experimental  Meningitis  in  Mon- 

73, 153 

keys"   

Journal  of   Experimental  Medicine. 

IX.     1907 

142 

FRANCA,  C.        .        .        . 

"Discussion  on   Cerebro-spinal  Me- 
ningitis, Sheffield" 

9 

Lancet.     Vol.  n.     1908 

478 

GEE,  S.  J.  AND  BARLOW,  T. 

"On  the   Cervical   Opisthotonos   of 

Infants" 

St  Bartholomew's  Hospital  Reports. 

9,  59,  91 

Vol.  XIV.     1878 

23 

GERVIS,      H.,      StTRGEON, 

ASHBTJRTON 

"Account    of   a   singular   and   fatal 
disease  occurring  in  several  persons 

6 

in  the  same  hamlet"     . 

Med.  Chir.  Trans.     Vol.  n.     1S17 

236' 

GOODWIN.     JI.     E.     AND 

SHOLLT,  A.  J.  Von       . 

"The  frequent  occurrence  of  meningo- 
cocci   in    the    nasal    cavities    of 
Meningitis  patients  and  those  in 

124 

direct  contact  with  them"  . 

Joum.    Inf.    Dis.     Supp.   n.     Feb. 

1906 

21 

GORDON,  M.  H. 

"  Epidemic     Cerebro-Spinal    Menin- 
sitis" 

142,  147 

Loc.  Got.  Board  Report.     1907 

94 

"Identification     of     the     Meningo- 

165 

coccus"         

R.A.M.C.  Journal.    Vol.  xxiv.    1915 

455 

GORDON,    M.    H.    akd 

MURRAY,  E.  G.     . 

"Identification     of     the     Meningo- 
coccus"          

165,  166 

R.A.M.C.  Journal.     Vol.  xxv.     1915 

411 

Bibliography  and  Index  of  Autliors 


201 


Title  of  Reference 


HALLIBURTON,  W.  D. 


HEEVLiN,   H.   AITD   FELD- 
STEIN,  S.        .        .        . 


HEUBNER,  0. 


BORDER,  T.  J. 
HORN,  A.  E. 


HOUSTON,  T. 
KIN,  J.  C. 


"Cerebro-Spinal  Fluid"     . 

Joum.  of  Physiology.     Vol.  x.     1889 

Meningococcus    Meningitis.       PhOa- 
delphia.     1913      .         .         .         . 


"  Beobachtungen  und  Versuche  iiber 
den  Meningokokkus  intraceUu- 
laris  (Weichselbaum,  Jaeger)" 
JahrbuchfiirKinderheilk.  XLm.  1S96 
Treatise  on  Geographical  and  His- 
torical Pathology,  translated  by 
Creighton.     1886  .        .         .         . 


Cerebro-spinal  Fever.     1915 

"Cerebro-Spinal  Meningitis  in  the 
Northern  Territories  of  the  Gold 
Coast". 

Society  of  Tropical  Medicine  and 
Hygiene  B.M.J.     Vol.  n.     1908 


J.AEGER,  H. 


JOCHMANN,  G. 


KEEN,  W.  W. 
KER,  C.      . 


KERNIG  OF  Pethogead 


KIEFER,  F. 


"Opsonic  and  Agglutinative  Power 

of  blood  serum  in  Cerebro-spinal 

Fever"  ..... 

B.M.J.     Vol.  n.     1907 

Die    Cerebro-spinal    Meningitis    als 

Heereseuche.     Berlin.     1901. 
Die     specifisohe    Agglutination    der 

Meningokokken  u.s.w.  . 
Zschr.   f.  Hyg.   u.  Infektionskrank. 

XLiv.     1903 
"Versuch    zur    Serodiagnostik    und 

Serotherapie  der  Epidemische  Ge- 

Deutsch.  Med.  Woch.     No.  20.     1906 

AmericanText-book  of  Surgery.  VoLi. 
1893 

"The   Treatment   of   Cerebro-Spinal 

Meningitis  with  Flexner's  serum" 

Edinburgh  Medical  Journal,  i.  1908 

"A  Review  of  Recent  Work  on  Epi- 
demic Cerebro-spinal  Meningitis" 
Practitioner.     xx\Ti.     1908 

"Ueber  ein  wenig  bekanntes  Symptom 
der  Meningitis  von  Kemig" 

(Wratsch  1884,  No.  26-27  Russisch) 
Neurologisches  Centralblatt  1884. 
Dritter  Jahrgang 

"Zur  Differentialdiagnose  des  Erre- 
gers   der   Epidemischen   Cerebro- 
spinal Meningitis  und  der  Gonor- 
hoe"     ...... 

Berl.  Klin.  Woch.     xxxm.     1896 


1 

156 
238 


547 
549 
555 
564 
104 
167 


306 


1 

30 
73 
91,  142 


23,  30,  58 

84 

10,  11 


91,  142 
91 


53 
53,73 

53,73 

22 


202 


Bibliography  and  Index  of  Authors 


Title  of  Reference 


LEES,  D.  B.  ASD  BARLOW, 
Sib  Thomas 


LIEBERIIEISTER.  G.  asd  1 
LEBSANFT,  A. 


VON  LINGELSHEDI 


LOW,  G.  C.         .        . 
LOWE,  G.  II.  or  Liscoln 


LUNDIE,  THOMAS, 

TLEMING     ANT3      JIAC- 
LAGAN    .        .        .        . 


macdonald,  s. 
McDowell,  j.  e. 


MACEWEN,  SiK  WiLOAJt . 


McGregor 

MACKENZIE,  L  and  MAR- 
TIN, W.  B.      . 


MATTHEY,  A.    . 


MAYER,        WALDMANN, 
FiJRST  and  GRUBER  . 


"Simple  Meningitis  in  Children" 
Allbutt's  System  of  Medicine.     Vol. 
vn.     1899 

"Ueber  Veranderungeu  der  nervosen 

Elemente     an     Riickenmark    bei 

Meningitis     Cerebrospinalis     Epi- 

demiea"        ..... 

Miinch.  Med.  Woch.     Lvl.     1909 

"Berichte  iiber  die  in  der  Hygien- 

ische  Station  zu   Beuthen,   0.   S. 

Torgenommenen  bakteriologischeu 

Untersuchungen  bei  Epidemische 

Geniekstarre "        .... 

Deutsch.  Med.  Woch.     1905 

"The       Treatment       of       Epidemic 

Cerebro-spinal  Meningitis". 

B.M.J.     Vol.  I.     Feb.  27,  1915 

"On  an  epidemic   of  Cerebro-spinal 

Meningitis"  ..... 

Lancet.     Vol.  i.     1867 


'Cerebro-Spinal  Jleningitis,  Diag- 
nosis and  Prophylaxis :  Its  Re- 
cognition and  Treatment"  . 

B.M.J.     Vol.  I.     1915 


"  Observations      on     Cerebro-spinal 
Meningitis"  .         .         .        ,         . 

Joum.  of  Path,  and  Bact.     xn.  1908 

"Observations  on  a  pecuhar  type  of 

nervous  fever  characterisied  by  a 

functional     excitement     of      the 

Cerebro-Spinal  nerves" 

London  Journal  of  Medicine.     1851 

PvTogenic    Infections   of    the    Brain 
"  and  Spinal  Cord.     1893 


Sue  Currie  and  McGregor 

"Serum  Therapy  in  Cerebro-Spinal 

Fever"  ..... 

Journ.  of  Path,  and  Bact     Vol.  sn. 

1908 
"Sur  une  Maladie  Particuliere  qui  a 

regne  a  Geneve  en  1805" 
Journal     de     Medecine,      Chirurgie,  1 

Pharmacie.    Paris.    January,  1806 

"Ueber  Geniekstarre  besonders  die  i 

Keitntrager  Frage"       .         .         .  i 

Miinch.  Med.  Woch.     L^-II.     1910 

"On  Cerebro-spinal  Arachnitis" 

Dublin  Quarterly  Journal  of  Medical 

Science.     Vol.  n.     1846  1 


1017 
1217 


146 
147 


466 
493    ( 
628 
836    \ 


153 
6 


120 
6 


Bibliograpluj  and  Index  of  Authors 


203 


Page  in 

Author 

Title  of  Reference 

Refer- 

Page 

ence 

MEAKESrS,  J.  C. 

"The  Method  of  fixation  of  Comple- 
ment in  the  Diagnosis  of  Meningo- 
coccus and  Gonococcus  Meningitis  " 

Johns    Hopkins    Hospital     Bulletin. 

107 

Vol.  x^-in.     ISIOT 

255 

MELA,  GirsEPPi 

"Commento  suUa  Spinite  Epidemica 
che  re2:no  in  Alassio  e  suoi  con- 
tomi  nd  ISli."     Torino.     1815    . 

Quoted  by  Corradi,  Annali  delle  Epi- 
demiclie   occorse   in   ItaUa.     Vol. 

4 

vn.     Appendice 

963 

MORGAN,  D.       .         .         . 

An  Account  of  an  outbreak  of  Spot- 
ted FeTer  which  occurred  in  Swan- 
sea during  1908.     Swansea.    1909 

76,  77,  78 

NETTER,  A.  asd  DEBEfi, 

R 

La  Meningite  Cerebro-Spinale.   Paris. 

5 

5 

1911 

101 

20 

154 

41 

114 

42 

154- 

220 

43 

154- 

221 

44 

21 

63 

84 

64 

208 

68 

112- 

207 

69 

209 

70 

209 

71 

255 

256 
257 

■80 

258 

1 

257. 

81 

257 

82 

223 

99 

146 

113 

183 

117 

32 

124 

NORTH,  Elisha 

Treatise  on  a  Malignant  Epidemic 
called  Spotted  Fever.    New  York. 
1811 

4 

ORMEROD,  J.  A.       . 

"Epidemic  Cerebro-spinalMeningitis" 
AUbutt  and  RoUeston's  System  of 

6 

Medicine.     Vol.  i.     1905       . 

923 

App. 

939 

OSLER,  Sm  William  .       . 

"Discussion  on  Epidemic  Meningitis  " 
Proc.  Roy.  Soc.  Med.  Vol.  vm.  No.  5. 

8,  10,  74,  76 

1915 

41 

QUINCKE,  C.     .        .        . 

"Ueber  Hydrocephalus"  . 
Verhand.    d.    Cong.    f.    Innere   Med. 

28 

X.     1891 

321 

Die    Technik    der    Lumbalpiinktion. 

28,  34, 

Berlin.     1902      .... 

108 

204 


Bibliography  and  Index  of  Autltors 


Author 

Title  of  Refei-encc 

Page  in 
Refer- 
ence 

Page 

RANDOLPH,  R.  L.    . 

"A  Clinical  Study  of  Forty  Cases  of 
Cerebro-Spinal     Meniugitis     with 
reference  to  Eye  Symptoms" 

Bulletin    Johns    Hopkins    Hospital. 
Vol.  IV.     1893 

59 

24 

REECE,  Sttkgeon  Col.  E-  J. 

"  Notes  on  the  prevalence  of  Cerebro- 
spinal   Fever    among    the    civil 
population  of  England  and  Wales 
during   the   last   four   months   of 
1914   and   first   six    of    1915,    to- 
gether with  a  short  account  of  its 
appearance    among    troops" 
R.A.M.C.  Journ.     Vol.  xxiv.     1915 

555 

10 

RIST,  A.  AND  PARIS,  A.  . 

"Contribution  a  I'etude  chnique  et 
experimentale  a   diplococques   de 
Weichselbaum "     .... 

Bulletin  de  I'lnstitut  Pasteur.     Tome 
n.     1904 

338 

154 

ROBE,  GARDNER     . 

"  Discussion  on  Cerebro-Spinal  Menin- 
gitis, Sheffield"     .... 
B.M.J.     Vol.  n.     1908 
"Discussion  on  Epidemic  Meningitis" 
Proc.    Roy.    Soc.    Med.      Vol.    ix. 
No.   1 

1341 
5 

9,  10,  74 

30.  74,  76, 
128 

ROLLESTON,  Sueg.   Gen. 

H.  D 

"Discussion       on       Cerebro-Spinal 
Meningitis" 

Proo.    Roy.    Soc.    Med.      Vol.    ix. 
No.  1 

12 

74,  SO,  84. 

85 

ROUS,  PEYTON 

Quoted  by  Heiman  and  Feldstein      . 

163 

108 

SASSI,   GlACINTO 

"Saggio  sulla  spinite  epidemioa  che 
ha   regnato  in   Albenga  e   paese 
convicini    neUa     primavera     nel- 
I'anno  1814."     Genova.     1815     . 

Quoted    by    Corradi,    Annali    delle 
Epidemiche     occorse     in     Itaha. 
Vol.  vn.     Appendice 

962 

4 

SCOTT,  John      . 

"Epidemic  of  Cerebro-spinal  Menin- 
gitis at  Sunderland  in  18.30" 

Medical  Times  and  Gazette.     Vol.  i. 
1865 

515 

6 

SHIRCORE,     J.     V.     AND 

ROSS,  P.  H.    . 

"Epidemic  Cerebro-spinal  Meningitis 
in  Nairobi" 

Trans.   Soc.   Tropical  Medicine  and 
Hygiene.     1913 

83 

84 

SOPHIAN,  A.      .        .        . 

Epidemic  Cerebro-spinal  Meningitis. 

London.     1913      .... 

pref. 
136 
175 
152 
153 
58 
58 
102 
101 
53 
147 

9 

27 
30 

[34 

41 
43 
52 
53 
63 
71 

Bibliography  and  Index  of  Authors 


205 


Title  of  Refcre 


I  Page  ill 
Refei- 


SOPHIAN,   A. 


Epidemic  Cerebro-Spinal  Meningitis. 
London.     1913     .         .         .         . 


STILL,  G.  F. 


TRAVERS  SMITH,  R.  ahd 
JOYCE,  R.  D.         .        . 


UHTHOFF,  W.  . 


VEDDER,  E.  B. 
VIEUSSEUX,  M. 


VINES,  H.  W   C. 


WEICHSELBAUM,  A. 


"The  Bacteriology  of  the  Simple 
Posterior  Basic  Meningitis  of 
Infants" 

Journal  of  Path,  and  Bact.  Vol.  v. 
1898 


"Experiences    of    an    Epidemic    of 
Cerebro-apinal  Meningitis"  . 

Practitioner.     March,  1903 

"Ueber  das  Augensymptom  bei  epi- 

demische  C4enickstarre " 
Ber.  d.  xxxn  Versam.  d.  Ophthakn. 

GeseU.     1905 

useful     Culture 


"Starch     Agar 

Medium"       .         .         .         .         . 

Joum.of  Inf.Dis.x\^.  No.  3.  May,  1915 

"  Sur  la  maladie  qui  a  regne  a  Geneve 
au  Printemps  de  1805"  ,         , 

Journal  de  Medecine;  Chirurgie, 
Pharmacie.  Paris.  December, 
1905.     Frimaire  An   xiv 

"A  Starch  Medium  for  the  identifica- 
tion of  the  Meningococcus  by  its 
Sugar  Reactions" 

R.A.M.C.  Journal.     Vol.  xxv.    1916 

"Ueber  die  Aetiologie  der  akuten 
Meningitis  Cerebro-SpinaUs " 

Fortschritte  der  Medicin.  V.  Jahr- 
gang.     1887 


211 

219 

211 

219 

208 

209 

219 

220 

221 

219 

220 

221 

192 

43 

40 

152 

206 

213 

214 

113 

58 

61 

132 

43 

40 


79 

;so 


'r  82 

84 
I  107 

I  109 

I  110 

113 

117 

j  lis 

I  167 

8,  59,  91,  103 


150 
2 


1,  28,  59, 

>  90,  91,  142, 

149, 153 


206 


Bihliograpliii  and  Index  of  Authors 


Page  in 

Author 

Title  of  Reference 

Kefur- 

Page 

WEICHSELBAUM,  A. 

'■  Zur  Frage  der  Aetiologie  unci  Patho- 
genese  der  Epidemischen  Genick- 
starre".         .         .        ~;         .         . 

162 

Wien.  Klin.  Wooh.     1905 

992 

WEST,  C.  E.       . 

"The  bacteriology  of  chronic  post- 
nasal catarrh"     _. 
Proc.    Roy.     Soc.     Med.     Otological 

133 

section.     Vol.  iv.     1911 

44 

WESTENHOFFER,  M.       . 

"  Pathologische  Anatomic  und  Infek- 
tionsweg  bei  der  Genickstarre  "     . 

105 

Berl.  KUn.  Woch.     Bd  xlu.     1905 

737 

"Ueber    den    gegenwartigen    Stand 

105 

unserer  Kenntniss  von  der  iiber- 

tragbaren  Genickstarre" 

Berl.  Klin.  Woch.     Bd  XLiu.     1906 

1267 

"  Ueber  die  Praktische  Bedeutung  der 

105 

Rachenerkrankung  bei  der  Genick- 

starre"            

Berl.  KUn.  Woch.     Bd  XLiv.     1907 

1213 

WILKINSON,  Col.     . 

"  Discussion  on  Cerebro-Spinal  Menin- 
gitis"     

Proc.    Roy.    Soc.    Med.     Vol.    viii. 

11 

No.  5.     1915 

81 

WHITTLE,  E.     .        .        . 

"Varieties  in  the  type   of  ordinary 
fever  in  Liverpool" 

6 

London  Medical  Gazette.     1847 

807 

WOLLSTEIN,  M. 

"The    Para-Meningococcus    and   its 

anti-serum" 

Journal   of   Experimental   Medicine. 

166,  167 

Vol.  XX.     1914 

201 

"Biological  Relationships   of   Diplo- 

167 

cocous   Intraoellularis  and   Gono- 

coccus"         

Journal   of   Experimental   Medicine, 

Vol.  IX.     No.  5.     1907 

1 

WOOLLEY,  G.  N.      . 

"On  an  epidemic  of  Cerebro-Spinal 
Meningitis  at  Bardney" 

7 

Lancet.     Vol.  ii.     1867 

130 

WYNTER,  W.  E. 

"  Four  oases  of  Tubercular  Meningitis 
in  which  Paracentesis  of  the  Theca 
VertebraHs  was  performed  for  the 
relief  of  fluid  pressure  " 

30 

Lancet.     Vol.  ii.     1891 

981 

GENERAL   INDEX 


Abdominal  reflexes,  23 

Abortive  oases,  49 

Absence  of  pus  in  hydrocephalus,  102 

Absorption  of  cerebro-spinal  fluid,  path  of,  96 

„  tests,  164 

Acclimatization,  importance  of,  in  susceptibility,  127 
Accumulative  stage,  43,  117 
Acute  fatal  tjrpe,  44 

„  „         „      course  of,  65 

.,         „         ,,      morbid  anatomy  of,  98 
„      forms,  41 

„  ,,       gradual  recovery  of,  51 

„       type  with  recovery,  47 
Adenoids  as  nidus  for  meningococcus,   122 
Adhesions  in  cord,  53 

„  in  sub-arachnoid  space,  109 

Adynamic  state,  in  hydrocephalus,  55,  67 
„  „       in  suppurative  type,  50 

„  ,,      indication  for  puncture,  82 

„  ,,       value  in  prognosis,  67 

Age,  importance  of,  in  infection,  127 

,,      of  patient,  value  in  prognosis,  68 
Agglutination  reactions,  162 

„  „         classification  by,  147 

,,  „         macroscopic  method,  163 

Agglutinative  power  of  patients'  serum,  78,  106 
Agglutinins,  specific,   164 
Albenga,  first  epidemic  period  in,  4 
Albumen,  increase  of,  in  cerebro-spinal  fluid,  112 
Alternation  of  good  and  bad  days  in  hydrocephalus,  59,  67 
Ambulatory  cases,  43 
Anaesthesia,  daily,  not  harmful,  81 

„  general  for  lumbar  puncture,  30 

„  „         „    serum  injection,  79 

local,  31 
Anaphylactic  symptoms,  80 
Anatomy  of  membranes  of  brain,  92 
„  „  of  cord,  94 

Ankle  clonus,  23 

Anorexia  at  onset  of  acute  tjrpe,  47 
Antiphlogistic  treatment,  72 
Apathy  in  hydrocephalus,  56 
Aphonia,  26 

Apnoea,  in  posterior  basic  meningitis,  60 
Appetite,  loss  of,  at  onset,  13 
Apyrexial  periods,   16 

,,  ,,       in  cases  with  gradual  recovery,  52 

Arthritis,  morbid  anatomy  of,  104 

,,  treatment  of,  87 

Arthropathies,  25 
Aspect,  in  early  stage,  18 
Aspirin,  for  headache,  87 
Attendants,  risks  to,  131 


208  General  Index 

Attitude  of  patient  in  early  stages,  18 
Auricular  fibrillation,  27 
Autolytic  ferment,  150 
Auto-sedimentation,  163 

Babinski's  plantar  reflex,  23 

Back,  pain  in,  see  Pain  in  back 

Bactericidal  power  of  patient's  serum,   107 

Bacteriological  characteristics  of  cerebro-spinal  fluid  an  indication 

for  puncture,  81,  82 
Baflfling  symptoms,  period  of,  48,  64 
Barometer,  changes  in  relation  to  disease,  129 
Bath,  treatment  by  warm,  73 
Bedclothes,  disinfection  of,  85 
Bed  sores,  prevention  of,  85 
Belfast  epidemic,  9 
Blot's  breathing,  in  acute  fatal  type,  45 

,,  ,,  in  posterior  basic  meningitis,  60 

Bismuth,  for  vomiting,  87 
Bladder,  necessity  for  care  of,  86 
Blindness,  in  posterior  basic  meningitis,  60,   104 

,,  as  sequel  in  adults,  70 

Blisters,  in  earUer  methods  of  treatment,  72 
Blood,  meningococcus  in,   104 

,.       agar,  best  medium  for  meningococcus,  149 

cultures,  105,  117 
,,       pressure,  changes  during  puncture,  34,  110 
„  „  „  ,,       serum  injection,  77,  79,  110 

Biain,  anatomy  of  membranes  of,  92 
Brandy,  in  treatment,  86 
Breathing,  Biot's,  in  acute  fatal  type,  45 

„  ,,        in  posterior  basic  meningitis,  60 

„  cerebral,  18 

„  ,,         in  posterior  basic  meningitis,  60 

„  Cheyne-Stokes,   18 

„  „  in  acute  fatal  type,  46 

,,  ,,  in  fulminating  type,  42 

Bromidia  for  sleeplessness,  87 
Bronchitis,  26 
Broncho-pneumonia,  26 

„  „  in  sub-acute  type,   101 

Cape  To^vn,  fourth  epidemic  period  in,  8 
Capsules,  around  meningococci,  148 
Carpliology,  in  acute  stage,  15 
„  in  hydrocephalus,  56 

„  value  in  prognosis,  67 

Carriers,     definition  of,   121 
,,  discovery  of,   132 

,,         examination  of  throat  of,  137 
„  importance  of,  in  propagatmg  disease,  3,  11 

,,  in  normal  communities,   120 

„  temporary  and  prolonged,  136 

test  for,   165 
„  variations  in  numbers  of,   120 

Cases,  meningococcus  in  throat  of,  124 
Catarrh,  naso -pharyngeal,  26 
Catarrhal  stage,   122 
Causative  agent,  90 

Cellular  changes  in  cerebro-spinal  fluid,  112 
Cerebral  abscess,  differential  diagnosis  of,  38 
„         breathing,   18 

„  „  in  posterior  basic  meningitis,  60 

Cerebro-spinal  fluid,  alteration  of  chemical  constituents  of,  111 


General  Index  209 

Cerebro-spinal  fluid,  at  onset,  prognostic  value  of,  60 

causes  of  increased  pressure  in,  103 

cellular  changes  in,   112 

circulation  of,  96,  103 

complete  evacuation  desirable,  81 

differential  count  of  cells  in,  113 

importance  of  study  of,  108 

in  acute  fatal  type,  46 

,,         type  with  recovery,  48 
in  influenza,  35 
in  suppurative  type,  51 
in  tubercular  meningitis,  37 
inciease  in  sub-acute  type,   100 

„         of  albumen  in,   112 
incubation  of,  114 
normal,  108 

reducing  substance  in,   109 
unrelieved  tension  of,  causing  sequelae,  71 
yellow,  111 
Chains,  false,  of  gram-negative  cocci,   141 
Chemical  constituents  of  cerebro-spinal  fluid,   108 

„  ,,  ,,  ,,      alterations  in,  111 

Cheyne-Stokes  breathing,  18 

,,  ,,  in  acute  fatal  type,  46 

„  „  in  fulminating  type,  42 

Children,  chief  incidence  among,  128 

Choroid  plexus,  secretory  scource  of  cerebro-spinal  fluid,  96 
Chronic  meningitis,  56 
„        types,  50 

„  „       intermittent  form,  67 

„  ,,       morbid  anatomy  of,   101 

Circulation  of  cerebro-spinal  fluid,  96 
Cisternae  of  brain,  anatomy  of,  93 
Classification,  by  agglutination  reactions,   147 
;,  of  Elser  and  Huntoon,  147 

,,  of  gram-negative  cocci,   144 

Climate,  influence  of,  11 
Clot,  gelatinous,  m  cerebro-spinal  fluid,   112 
Clothing,  effect  of  shortage  of,   126 
,,  spread  of  disease  by,   130 

Cold  incubator  test,  at  23°  C,   146,   152,   158 
Coliform  organism,  with  colony  like  meningococcus,   144 
Colony,  appearances  of,  of  giam-negative  cocci,  143 

,,  ,,  of  meningococcus,   151 

Coma,  headache  replaced  by,  14 
„       in  acute  stage,  15 

„         fatal  type,  45,  46 
-,  .,         type  with  recovery,  48 

,,       in  fulminating  type,  41 
.,       on  third  day,  65 
Complement  fixation  of  patient's  serum,  107 

.,  ,,        tests  to  differentiate  meningococcus,  167 

Complications,  rarity  of,  in  adults.   103 
Compression  in  acute  fatal  type,  46 
Conditions  of  epidemic  outbreak,   125 
Congestion  of  cerebral  vessels  in  acute  fatal  type,  98 
,i  ,,  ,,        in  fulminating  type,  98 

Conjunctivitis,  24 
Constipation,  27 
Contact,  definition  of,   121 
„         isolation  of,   133 
Contagion,  direct,   119,   138 

Contamination,  by  gram-negative  cocci  of  air,   142 
Convalescence,  early  establishment  of,  66 

F.  &  G.  14 


210  General  Index 

Convalescence  from  other  diseases,  onset  during,   14 
Convalescents,  as  carriers,   124 

Convulsions,  at  onset  of  posterior  basic  meningitis,  59 
„  in  acute  fatal  type,  45,  46 

,,  in  fulminating  type,  41 

Cord,  anatomy  of  membranes  of,  94 
Corfu,  second  epidemic  period  in,  6 
Corn-starch  medium,   150 

,,  sugar  medium,   160 

Coryza,  onset  of  acute  type  preceded  by,  47 
Course  of  the  disease,  64 
Crisis,  in  cases  with  gradual  recovery,  51 

,,       termination  by,  66 
Cultural  characteristics,  91 
Culture  of  cerebro-spinal  fluid,   115 
„        of  menmgococcus.   149 

„  ,,  an  indication  for  puncture,  82 

„  „  from  post-mortem  material,  102 

Cupping,  in  earlier  methods  of  treatment,  72 
Curschmaun's  solution,  hypodermic  use  of,  87 
Cyanosis,  27 

„  in  acute  fatal  type,  46 

„  in  fulminating  type,  42 

„         value  in  prognosis,  67 
Cystitis  in  hydrocephalus,  102 

Dangers  of  lowering  cerebro-spinal  pressure,  82 

„        of  serum  injection,  79 

„        of  transport  negligible,  85 
Deafness,  24 

,,  in  convalescence,  70 

„  in  posterior  basic  meningitis,  61 

Definition  of  cerebro-spinal  fever,  1 
DeHrium,  coexistent  with  headache,  15 

„  in  the  acute  stage,  14 

,,  in  acute  fatal  type,  45 

„  „      type  with  recovery,  47 

.,  in  fulminating  type,  41 

„  in  hydrocephalus,  56 

„  maniacal,  in  acute  fatal  type,  45 

„  on  third  day,  65 

„         value  in  prognosis,  67 

„  tremens,  differential  diagnosis  from,  40 

„  „         onset  simulating,  15 

Denmark,  second  epidemic  period  in,  6 
Desiccation,  effect  on  meningococcus,  119,  152 
Despatch  of  swabs,  uselessness  of,   135 
Diagnosis,  28 

„  differential,  34 

„  „  dependent  on  bacteriology,  91 

,,  in  the  post-mortem  room,  102 

Diarrhoea,  at  onset,   14,  27 

Differential  count  of  cells  in  cerebro-spiaal  fluid,   113 
Diplopia,  23 
Direct  infection,  124 
Discharges,  di-infection  of,  85 

,,  purulent  from  nose  and  throat,  26 

Disinfectants,  effect  on  menmgococcus,  153 
Disinfection  of  discharges,  85 

,,  of  linen,  etc.,  132 

Disseminated  sclerosis  simulated  by  convalescent  cases,   23 
Dosage  of  serum,  80 
Drainage  normal,  re-estabUshment  of,  58 

re-establishment,  the  cause  of  crisis,  66 


General  Index  211 


Dry  tap,  33 

Drying,  effect  on  meningococcus,   119,  152 
Dyspnoea,  urgent  in  fulminating  oases,   18.  27,  42 
value  in  prognosis,  67 

Early  treatment,  importance  of,  65 

East  Africa,  epidemic  in,   11 

Edinburgh  epidemic,   10 

Emetics  in  earlier  methods  of  treatment,  72 

Endocarditis,  27,   104 

English  epidemic  of  1915,   10 

,,  ,,         Flexner's  sernm  in,  74 

Epidemics,  1 

,,  conditions  producing,   125 

Epidemic  periods,  3     • 

,.  stage  of,  value  in  prognosis,  69 

Erroneous  fermentation  results,   159,  160 
Erjrthema,  fugitive,  19 

,,  in  acute  fatal  type,  45 

Evacuation  of  cerebro-spinal  fluid  desirable,  complete,  81 
Exacerbations,  67 
External  hydrocephalus,  60 
Extracellular  cocci,  importance  of,   115 

.,  .,       value  in  prognosis,  fiS 

Failure  of  early  forms  of  treatment.  73 
,,        of  serum  treatment  in  1915,  76 
Fatigue,  influence  on  susceptibility,  128 
Feeding,  difficulty  in,  20 
„         nasal,  86 

„         of  hydrocephalic  cases,  56 
,,         rectal,  86 
Fermentation  reactions,  characteristic  rates  of,   146,   158 
„  ,,  of  gram-negative  cocci,  160 

„  „  of  meningococcus,  161 

„      ^  ,,-         of  micrococcus  catarrhalis,  162 

„  ,,  use  in  classification,  144,   158 

Fever,  indication  for  puncture,  82 

„       intermittent    in  acute  type  with  recovery,  49 
,,       resemblance  to  ague,  16,  52 
,,       value  in  prognosis,  67 
Fifth  epidemic  period,  8 
Fijian  Islands,  fourth  epidemic  period  in,  8 
Film  preparations,  importance  of  number  of  cocci  in,  115 
„  „  meningococci  in,   113 

„  „  staining  of,  114 

First  clinical  description,  2 
„      day  of  iUness,  64 
,,      epidemic  wave,  3 
Flaccid  paralysis,  23 
Flexner's  serum,  73 

Fluid  culture,  growth  of  meningococcus  in,  150 
Foreign  proteid,  introduction  of,  in  serum  treatment,  77 
Four  groups  of  Gordon,   165 
Fourth  epidemic  period,  8 

„        ventricle,  adhesion  of  roof  of,  58,   102 
France,  first  epidemic  wave  in,  4 
,,        second  epidemic  wave  in,  4 
,,        fifth  epidemic  wave  in,  9 
Frequency  of  serum  injections,  81 
Fulminating  type,  41 

„  „      microscopical  pathology  of,  98 

,,  ,,      morbid  anatomy  of,  97 

„  „      nature  of,  42 

14—2 


212  General  Index 

Fulminating  type,  onset  of,  13 

Gee  and  Barlow's  disease,  59 

Gelatinous  clot,  in  oerebro-spinal  fluid,   112 

General  reaction  of  body,   105 

General  treatment,  85 

Geneva  epidemic,  2 

Geograpliical  distribution,   11,   129 

Germany,  third  epidemic  wave  in,  7 
,,  fifth  epidemic  wave  in,  9 

Glasgow  epidemic,   10 

Glucose  in  cerebro-spinal  fluid,  109 

„  „  „      diminution  of,   112 

Gonococcal  meningitis,  doubtful  occurrence  of,  144 

Gonococcus,  characters  of,  146 

,,  differentiation  from  meningococcus,  144 

Gordon's  four  groups,  165 

Gram's  stain,  method,   141 

Gram-negative  diplococci,  gram -positive  foims  of,  142 
of  the  air,  142 
„  „  the  group  of,   139 

Gram-positive  cocci  of  Jaeger  and  Heubner,  142 

,,  forms  in  meningococcus  cultures,   148 

,,  ,,       of  the  gram-negative  cocci,   142 

Granular  staining  of  meningococcus,  148 

Greece,  third  epidemic  period  in,  7 

Group  agglutinations,  164 

Grouping  of  strains,   165 

Haematogenous  origin  of  disease,   153 
Haematuria,  27 

Haemophilia,  exclusion  of  meningeal  haemorrhage  in,  S 
Haemorrhage,  meningeal,  differential  diagnosis  of,  39 
Head,  nodding  of,  21 
„       retraction  of,  21 

„  „  absent  in  fulminating  t3'pe,  42 

„  „  in  acute  fatal  t3'pe,  45 

I,  ,,  ,,         typs  with  recovery,  48 

„  „  in  hydrocephalus,  56 

„  „  in  posterior  basic  meningitis,  60 

„  „  index  of  intracranial  pressure,  49 

„  „  on  third  day,  65 

,,  „  value  in  prognosis.  67 

Headache,  an  indication  of  increased  pressure,  57 
„  „  for  puncture,  81,  87 

„  at  onset,   14 

„  co-existent  with  delirium,   15 

„  in  acute  fatal  type,  44 

„  ,,         type  with  recovery,  47 

„  in  convalescence,  70 

„  in  hydrocephalus,  55 

,,  intense  in  fulminating  form,  41 

,,  on  first  day,  64 

„  treatment  of,  86 

Heart,  little  toxic  effect  on,   154 
Hemiplegia,  23 

,,  in  acute  fatal  type,  45,  40 

Herpes,  20 

„        in  acute  fatal  type,  46 
,,  „         typG  \vith  recovery,  48 

,,        value  in  prognosis,  68 
Hexamine,  treatment  by,  85 
Hirsch's  four  epidemic  periods,  3 
His'  medium,  160 


General  Index  213 

History,  1 

Hydrocephalic  cry,  in  posterior  basic  meningitis,  60 

„  symptoms,  following  scrum  injection,  77 

Hydrocephalus,  53,  54 

,,  absence  of  cocci  in  cerebro-spinal  fluid  of,  103,  116 

„  ,,  pus  in,  102 

„  amoimt  of  pus  in,  111 

„  established  in  second  or  third  week,  67 

„  external,  60 

„  in  posterior  basic  meningitis,  59 

„  morbid  anatomy  of,  101 

„  \vith  acute  stage  wrongly  diagnosed,  59 

„  „      recovery,  57 

Hydrocyanic  acid  for  vomiting,  87 
Hyperaesthesia,  23 

Hypersecretion  of  choroid  plexuses,  97 
Hypophysial  gland,  as  path  of  infection,  105 

Ice  to  the  head  in  treatment,  72,  78 
Iceland,  second  epidemic  period  in,  6 
Imbeciles,  25 

Improvement,  early  signs  of,  66 
Inagglutinable  strains,  163 
Incubation  of  cerebro-spinal  fluid,   114 

„  period,  62 

Incubator,  travelling,  135 
India,  outbreaks  in,  11 
Infection,  direct,  124 

„  distribution  of.  in  meninges,   102 

path  of,  104 

„  site  of,   100,   117 

Influenza,  cerebro-spinal  fluid  in,  35 

„  differential  diagnosis  from,  34 

„  increased  cerebro-spinal  pressure  in,  110 

Inhibition  of  growth  of  meningococci,  151,   152 
Inoculation,  subdural  in  animals,  153 
Intermittent  carriers,  136 

Intracellular  position  of  gram-negative  cocci,  143 
Intracranial  pressure,  increase  in  acute  fatal  type,  45,  46 

„  „  „  ,,  type  with  recovery,  48 

„  ,,  sudden  rise  at  onset,  14 

Intramuscular  injection  of  serum,  83 
Intrathecal  serum  administration  of  Flexner,  73 
Intravenous  injection  of  serum,  83 
Intraventricrdar  puncture  in  hydrocephalus,  117 
Iodide  of  potassium,  treatment  by,  73,  86 
Ireland,  third  epidemic  period  in,  7 
Iritis,  24 

Iridochoroiditis,  24 
Iridocyclitis,  24,  104 

Irregularities  in  size  and  staining  of  meningococcus,  140 
Isolation  of  contacts,  133 

„         of  patients,  130 

,,         of  prolonged  carriers,  136 
Italy,  second  epidemic  period  in,  5 

Jochmann's  serum,  73 

Keen's  operation  to  drain  ventricle,  89 
Keratitis,  24 
Kernig's  sign,  22 

„  ,,      importance  of,  on  second  day,  64 

„  „      in  acute  fatal  type,  45 

,,  .,  „        type  with  recovery,  48 


214  General  Index 

Kernig's  sign,  in  cases  of  gradual  recovery,  52 

in  fulminating  type,  42 

in  posterior  basic  meningitis,  60 

normal  in  infants,  22 

the  indication  of  meningeal  infection,  54 

value  in  diagnosis,  29 
Knee  jerks,  23 
Kocher's  operation  for  draining  ventricle,  89 

Landes,  the,  origin  of  second  epidemic  period  in,   4 

Large  and  small  colonies  of  meningococci.   151 

Lateral  sinus  thrombosis,  differential  diagnosis  of.  39 

Lateral  ventricle,  operations  to  drain,  88 

Leeches  in  treatment,  72,  87 

Leucoc3^osis,  105 

London,  fourth  epidemic  period  in,  8 

Lumbar  puncture,  anatomical  points  in,  95 

general  anaesthetic  in,  30 

in  acute  fatal  type,  46 

,,         type  with  recovery.  48 

in  adynamic  state,  55 

in  cases  of  gradual  recovery,  52 

in  hydrocephalus,  55,   103 

in  suppurative  type,  50 

indicated  by  Kernig's  sign,  23 

introduction  of,  28 

lateral  operation  for,  32 

operation  of,  29 

position  of  patient  for,  32 

remote  effects  of,  83 

symptoms  justifying,  28 

fluid,  sudden  diminution  in  hydrocephalus,  57 
Lysis,  termination  by,  66 

MacEwen's  sign,  56 

„  „      in  posterior  basic  meningitis,  60 

Macular  rash,   18 

„  ,,      in  acute  fatal  type,  36 

„  „  „        type  with  recovery,  48 

,,  ,,       value  in  prognosis,  68 

Manometer,  for  cerebro-spinal  fluid,  34 
Measles,  differential  diagnosis  from,  36 
Medico-legal  aspect  of  fulminating  case,  42 
Medulla,  pressure  on,  in  hydrocephalus,  56 
Membranes  of  brain,  anatomy  of,  92 

,,  of  cord,  anatomy  of,  94 

Meningitis,  gonococcal,  doubtful  occurrence  of,  144 

„  pneumococcal,  differential  diagnosis  from,  38 

,,  purulent,  differential  diagnosis  from,  38 

,,  staphylococcal,  differential  diagnosis  from,  38 

„  streptococcal,  differential  diagnosis  from,  38 

,,  tubercular,  cerebro-spuial  fluid  of,  37 

,,  ,,  differential  diagnosis  from,  37 

Meningococcus,  a  group  of  related  organisms,   107,  140 
„  characters  of,  146,  148 

,,  discovery  of,  28 

„  in  film  preparations,  113 

„  sugar  reactions  of,  161 

Mental  condition,  following  cerebro-spinal  fever,  25 
Mental  depression  in  isolated  carriers,  136 
Mental  enfeeblement,  58 
Mercury  in  treatment,  86 
Metachromatic  granules  in  meningococcus,  148 
Micrococcus  catarrhalis,  characters  of,   146,   157 


General  Index  215 

Jlicrococcus  catarrhalis,  in  posterior  pharynx,  140 
„  „  sugar  reactions  of,  162 

,.  flavus    I    chaiacters  of,  145,  156 

„  „        IT  .,  145    156 

„      III  „  146,  157 

,,  pharyngis  siccus,  characters  of,   145,  155 

Microscopical  pathology  of  acute  fatal  type,  99 
,,  ,,  of  fulminating  type,  98 

Micturition,  difficulty  of,  in  early  stage,  20 
Mild  oases,  absence  of  cocci  in  cerebro-spinal  fluid  of,  116 
Milk,  growth  of  meningococcus  in,  151 
Monoplegia,  23 
Morbid  anatomy  of  acute  fatal  type,  98 

.,  „         of  chronic  type  with  hydrocephalus,  101 

„  „         of  fulminating  type,  97 

.,  „         of  palsy  in  children,  104 

,,  „         of  sub-acute  type,   100 

,,  „         of  suppurative  type,  100 

Morphia  for  headache,  86 
.,  „    vomiting,  87 

,,  to  diminish  risk  to  attendants,  132 
Morphology  of  the  gram-negative  cocci,  140 
Mortality,  in  posterior  basic  meningitis,  61 

,,  severe  in  earlier  epidemics,  72 

Mumps,  differential  diagnosis  from,  36 
Muscles  of  neck,  stiffness  at  onset.  21 

.,  „  „         on  second  day,  64 

MiLscular  rigidity  at  onset,  21 

„  „        in  fulminating  type,  42 

„  „        in  hydrocephalus,  56 

„  „        on  third  day,  65 

Myelitis,  acute,  differential  diagnosis  from,  40 
Myocarditis,  27 

Nasal  cavity,  connection  with  sub -arachnoid  space,  94,  105 

„      douche,  137 

„      feeding,  86 

,,      irrigation,  necessity  of,  185 

„  ,,  „  „    for  attendants,  132 

Naso-pharynx,  meningococcus  in,  119 

„  ,,         of  cases,  meningococcus  in,  124 

Neck,  muscles  of,  stiffness  at  onset,  21 

,,  ,,  „         on  second  day,  64 

Needle,  Barker's,  for  lumbar  puncture,  31 
Nerve,  facial,  involvement  of,  23 

„       hypoglossal,  involvement  of,  23 

„       cells,  condition  of,  in  acute  fatal  type,  99 
Neutral  red  as  indicator,  159 
New  York,  epidemic  of  1905  in,  125 
Nomenclature,  1,  90 
Normal  communities,  carriers  in,  120 
Nourishment  in  acute  stages,  85 
Number  of  cocci  in    fihns,  effect  of  serum  on,  115 
,,  „  „      importance  of,  115 

,,         of  lumbar  punctures  necessary,  82 
Nursing,  precautions  in,  132 
Nutrition,  general  influence  on  infection,  127 
Nutrose  agar,  best  for  plates,  149 
Nystagmus,  23 

Occlusion  of  sub-arachnoid  space,  109 
Odyssey  of  18th  Light  Infantry,  5 
Olfactory  lobes,  in  acute  fatal  type,  98 
„  nerves,  as  path  of  infection,  104 


216  General  Index 

Onset,  64 

„        in  acute  fatal  tj^pe,  44 
,,  „        type  with  recovery,  47 

„       in  fulminating  type,  41 
„       of  hydrocephalus,  55 
,,       of  posterior  basic  meningitis,  59 
„       suddenness  of,  13 
Operations,  for,  hydrocephalus,  87 
Ophthalmia,  purulent,  24 
Opisthotonos,  22 

,,  in  posterior  basic  meningitis,  59,  60 

Opium  in  earlier  methods  of  treatment,  73 
Opsonic  index  of  patient,  106 

,,         tests  for  differentiation  of  meningococcus,   167 
Optic  atrophy,  24 

,,         after  soamin,  85 

„         rarity  in  posterior  basic  meningitis,  60 
discs,  in  hydrocephalus,  56 

lobes,  pressure  on,  in  posterior  basic  meningitis,  60 
neuritis,  24 

,,        in  posterior  basic  meningitis,  60 
Otitis  media,  25 

Overcrowding,  effect  on  individual,   126 
,,  importance  -  of ,  12 

Pacchionian  bodies,  absorption  through,  96 

„  „       anatomy  of,  92 

Pain  in  back,  as  sequela,  58 
,,  ,,      and  legs  iu  convalescence,  71 

,,  „         ,,     thighs  at  onset,  20 

Palsy,  23 

„       as  sequela,  58 

,,       in  children,  morbid  anatomy  of,  104 
„       in  convalescence,  70 
„       treatment  of,  87 
Panophthalmitis,  24,   104 
Para-meningocoocus,  characters  of,  146 

,,  differentiation  of,  166 

„  sugar  reactions  of,  161 

Path  of  infection,  104 

Pathogenicity  of  meningoooeous  to  animals,  153 
Pathology,  90 

Patients'  serum,  agglutinative  power  of,  78 
,,  ,,       intrathecal  injection  of,  78 

Perivascular  haemorrhage  in  acute  fatal  case,   1 
„  infiltration  of  brain,  99 

„  „       of  cord,  99 

Permanent  carriers,  136 
Petechial  fevers,  possible  identity  of,  2 
„         rash,  19 

,,        „     in  acute  fatal  type,  45 
:,  „     in  fulminating  type,  42 

,,  ,,     value  in  prognosis,  67  ' 

Pharyngitis,  differential  diagnosis  from,  36 
Pharynx,  posterior,  meningococcus  in,  104 
Photophobia,  as  an  early  symptom,  14 
Physical  conditions,  importance  in  culture^   150 
Pigmentation  of  cerebro-spinal  fluid,   112 

„  punctiform,  of  colonies  of  gram-negative  cocci,   143 

,,  ,,  of  meningococcus  colony,  150 

Plague  spot,  20 
Plantar  reflex,  23 
Plate  culture,  investigation  of,  167 
„  ,,        method  of  sowing  swab  on,  134 


General  Index  217 


Plate  holder,  sterilizable,   133 

Pleurisy,  27 

Pneumococcal  meningitis,  38 

Pneumococcus,  terminal  infection  by,  38 

Pneumonia,  differential  diagnosis  from,  35 

,,  increased  cerebrospinal  pressure  in,  110 

,,  lobar.  27 

Poisonings  suspicion  of,  in  fulminating  cases,  42 
Polioencephalitis,  differential  diagnosis  from,  40 
Pohomyelitis,  differential  diagnosis  from,  40 

„  not  differentiated  in  earl}'  epidemics,  7l 

Portugal,  fifth  epidemic  wave  in,  9 
Position  of  patient  for  lumbar  puncture,  32 
Posterior  basic  meningitis,  59 

„  „  ,,  a  disease  of  infants,  128 

„  „  ,,  chronic  course  of,  60,  61 

„  „  ,,  identity  with  chronic  type.   103 

,,  ,,  ,,  recognition  in  fifth  period.  8 

,,  „  ,,  usual  form  in  England,  91 

Posterior  pharynx,  meningococcus  in,  104 
Precipitin  reactions,   )67 
Predisposing  causes  of  infection,  125 
Pressure,  cerebro-spinal,  increase,  causes  of,  103 

„  „  „  in  the  disease.  109 

,  ,,  „  indicated  by  headache,  57 

„  ,,  ,,  other  diseases,  110 

„  „  normal,  108 

„  „  on  meduUa  in  hydrocephalus,  56 

„  ,,  replacement  of,  in  serum  treatment. 

Preventive  measures,   130 
Previous  illness,  a  predisposing  cause,  126 
Prognosis,  67 

„  remote,  70 

Prolonged  carriers,  121 

,,  „         isolation  of,  136 

Prostration,  prevention  of,  87 
Proteolysis,  by  meningococcus,  162 
Pseudo-meningococcus,  165 

,,  .  carriers,  168 

Pulse,  16 

„       during  serum  injection,  79 
,,       in  acute  fatal  type,  44 
„  „         type  with  recovery,  47 

„       in  fulminating  form,  42 
„       in  hydrocephalus,  55 
,,       irregularity  of,  17 
,,       respiration  ratio,  18 
„      running,  17 

,,       slow  with  high  temperature  at  onset,  17 
,,       value  in  prognosis,  67 
Pupils,  condition  of,  24 
Purpuric  rash,  19 

„  ,,     in  fulminating  tj^pe,  42 

,,  „      value  in  prognosis,  67 

Purulent  meningitis  early  in  disease,  43 
Pus,  amount  in  cerebro-spinal  fluid.  111 
Pyehtis,  27 
Pyrocatechin  in  cerebro-spinal  fluid,  109 

Rainfall,  in  relation  to  the  disease,  129 
Eash,  serum,  80 

J,       varieties  of,   18 
Ratio,  pulse-respiration,  18 
Rectal  feeding,  86 


218  General  Index 

Reducing  substance  in  cerebro-spinal  fluid,  109 
Reflexes,  abdominal,  23 
„         plantar,  23 
„         superficial,  23 
Relapse,  53 
Relapsing  cases,  58 

Relief  of  symptoms  after  puncture,  110 
Remote  prognosis,  70 

Replacement  of  pressure  in  serum  treatment,  77 
Respiration,  18 

Riot's,  IS 
,,  during  serum  injection,  79 

„  in  acute  fatal  type,  45 

„  „         type  with  recovery,  47 

„  in  fulminating  type,  42 

Respiratory  failure,  18 

„  „       due  to  increased  pressure,  110 

„  „       in  acute  fatal  type,  46 

Restlessness,  in  the  acute  stage,   15 
„  value  in  prognosis,  67 

Retention  of  urine  in  acute  fatal  type,  45 

,,  ,,  ,,     type  with  recovery,  48 

„  „      in  early  stage,  20 

„  ,,      in  fulminating  type,  42 

•  „  „      in  hydrocephalus,  55 

,,  „      value  in  diagnosis,  29 

Retraction  of  head,  21 

„  „      absent  in  fulminating  type,  42 

„  ,,      in  acute  fatal  type,  45 

„  ,,  „         type  with  recovery,  48 

„  ,,      in  hydrocephalus,  56 

„  „      in  posterior  basic  meningitis,  60 

,,  „      index  of  intracranial  pressure,  49 

„  „      on  third  day,  65 

,,  ,,      value  in  prognosis,  67 

Rigidity,  muscular,  at  onset,  21 

,,  „  in  fuhninating  type,  42 

,.  „  in  hydrocephalus,  56 

„  ,,  in  posterior  basic  meningitis,  60 

,,  ,,  on  third  day,  65 

Rigor  at  onset,  13,  64 

„      in  acute  fatal  type,  44 
„  „         type  with  recovery,  47 

„      in  fulminating  type,  41 
„      in  hydrocephalus,  55 
Russia,  third  epidemic  period  in,  7 

Scarlet  fever,  difi'erential  diagnosis  from,  36 
Screaming  at  onset  of  posterior  basic  meningitis,  59 
Seaport  as  starting  place  in  an  epidemic,  11 
Seasonal  distribution  of  disease,  129 

„         weather  conditions,  effect  on  susceptibiUty,  126 
Second  day  of  illness,  64 

„        epidemic  period,  4 
Septicaemia  in  early  stage,  43,  92 

„  initial,  as  path  of  infection,  105 

„  meningococcal,  42,  104,  117 

„  „  post-mortem  appearances  in,  97 

Septicaemic  stage,  122 
Sequelae  of  hydrocephalus,  58 

„         rarity  of,  71 
Serum,  dosage,  80 

„        injections,  frequency  of,  81 
„       intramuscular  injection  of,  83 


General  Index  219 

Serum,  intravenous  injection  of,  83 

,,        introduction  to  ventricles,  88 

„        methods  of  injection,  78 

„        of  patient,  bactericidal  power  of,  107 

„  ,.  intrathecal  injection  of,  52,  107 

rash,  80 

„        subcutaneous  injection  of,  83 

,,        treatment,  effect  on  cocci,  115 

,,  „  indications  for  suspension  of,  81 

Shifting  population,  importance  of,  12 

,,  ,,  in  epidemics,   125 

Shock,  during  serum  injection,  80 

,,       from  lumbar  puncture,  82 
Sicily,  second  epidemic  period  in,  6 
Sinuses  of  nose  as  harbours  for  meningococcus,  122 
Site  of  meningococcal  infection,  100 
Size  of  gram-negative  cocci,  variations  in,  140 
SmaU-pox,  differential  diagnosis  from,  36 
Soamin,  treatment  by,  84 
Sore  throat,  onset  preceded  by,  47 
Source  of  cocci  in  cerebro-spinal  fluid,  117 
Specific  agglutinins,  164 

„        fevers,  cerebro-spinal  fever  a  sequel  of,  36 
Sphenoidal  sinuses  as  harbours  of  meningococcus,  122 

„  ,,        as  path  of  infection,  104 

Sphincters,  involvement  of,  20 
Sporadic  appearance  of  disease,  123 

,,         cases,  1 
Spread  of  disease  by  prolonged  carriers.   121 

„      method  of,  130 
Spreading  of  plate  cultures,  135 
Spring,  cerebro-spinal  fever  a  disease  of,   129 
Stab  culture,  advantages  of,  150 
Stage  ot  epidemic,  value  in  prognosis,  69 
Staining  after  macular  rash,  19 

„         of  films  from  cerebro-spinal  fluid,  114 

,,         of  gram-negative  cocci,  140 
Staphylococcal  meningitis,  38 

Staphylococci,  gram-negative  cocci  belonging  to,  141 
Starch  medium,  150 

„       sugar  medium,  160 
Sterilizable  plate-holder,  135 
Sterilization  of  fluid  media,  difficulties  of,  158 
Stippling  of  meningococcus  colonj',  150 
Strabismus,  23 
Streptococcal  meningitis,  38 

Streptococci  with  colonies  lite  meningococcus,  144 
Strychnine,  hypodermic  use  of,  87 
Stupor  in  acute  stages,  15 
Sub-acute  types,  50 

„  ,,        morbid  anatomy  of,  100 

Sub-arachnoid  space,  anatomy  of,  92 

„  „        obstruction  of,  in  hydrocephalus,  57 

„  „        of  cord,  95 

,,  ,,        operation  to  drain,  89 

,,  „        prolongations  into  nose,  94,  105 

Sub-culture,  essentials  for,  150 

„  necessity  of,  from  sugar  media,  161 

Subcutaneous  injection  of  saline,  87    . 

,,  ,,  of  serum,  76,  83 

Sub-dural  inoculation  in  animals,  153 
Subsultus  tendinum  in  acute  stages,   15 

„  „  in  fulminating  type,  42 

„  „  in  hydrocephalus,  56 


220  General  Index 

Sugar,  in  cerebro-spinal  fluid,  109 

„  „  „      diminution  of,  112 

„       media,  composition  of,  169 

„  „       difficulty  of  sterilizing,  158 

solid,  159 
„       reactions,  cliaracteristic  rates  of,  146,  158 
„  „  of  gram -negative  cocci,  160 

„  ,,  of  meningococcus,  161 

„  „  of  micrococcus  catarrhalis,  162 

,.  ,,  use  in  classification,  144,   158 

Summer,  rapid  decline  of  epidemic  in,  129 
SunUght,  eflfeot  on  meningococcus,  152 

„  gram-positive  forms  produced  by,  143 

Superficial  reflexes,  23 
Suppurative  type,  50 

„  „      amount  of  pus  in,  111 

,,  „      course  of,  66 

,,  „      morbid  anatomy  of,  100 

Suprarenal  capsules,  haemorrhagic,  98 
Surgical  procedures  in  posterior  basic  meningitis,  61 
Susceptibility  of  individual,  changes  in,  125 
Suspension  of  serum  treatment,  indications  for,  81 
Swab,  convenient  form  of,  134 
„        method  of  taldng,  133 
„       uselessness  of  despatch  of,  135 
„       West's  covered,  133 
Swallow,  inability  to,  20 

,.  „  in  acute  fatal  type,  46 

„  ,,  ,,       .type  with  recovery,  48 

Sweating  in  acute  fatal  type,  46 
„  in  fulminating  type,  42 

Sweden,  third  epidemic  period  in,  6 
Symptoms,  13 

„  aggravation  of,  following  serum  injection,  77 

„  ,,  on  third  day,  46 

„  diminution  of,  on  second  day,  45 

„  justifying  lumbar  puncture,  28 

„  rehef  of,  after  lumbar  puncture,  110 

Tache  cerebrale,  24 

Tapping  the  ventricles,  operation  for,  88 

Temperature,  course  of,  in  the  disease,  16 

„  daily  variations  in  atmospheric,  129 

„  in  acute  fatal  type,  44 

„  „         type  with  recovery,  47 

„  in  fulminating  type,  42 

„  in  hydrocephalus,  55 

Temperatures  of  growth  of  meningococcus,  152 
Temporary  carriers,  121,  136 

,-  „         treatment  of,  136 

;,  improvement  on  second  day,  64 

Tenderness  in  muscles  of  neck  at  onset,  21 

,,  „  „      on  second  day,  64 

Terminal  invasion  in  hydrocephalus,  57 

„  ,,         in  posterior  basic  meningitis,  61 

Termination  by  crisis,  66 
„  by  lysis,  66 

Tetanus,  differential  diagnosis  from,  37 
Tetrads,  meningococci  in,   143 
Theca,  adhesion  of,  in  hydrocephalus,  102 
Third  day  of  iUness,  65 
„       epidemic  period,  6 
Throat,  local  treatment  of,  137 

„        normal,  meningococcus  in,  91 


General  Index  221 

Throats  of  cases,  meningococcus  in,  124 

„        of  nurses,  examination  of,  132 
Thrombosis  of  venae  Galeni  as  cause  of  hydrocephalus,  59 
TonsUhtis,  differential  diagnosis  from,  36 
Toxaemia,  in  acute  fatal  type,  45 

„  in  fulminating  type,  41 

Toxins  of  meningococcus,  154 
Transient  carriers,  121,  136 

,,  ,,         treatment  of,  136 

Transport,  dangers  of,  negUgible,  85 
Transvaal,  epidemic,  in,   11 
Travelhng  incubator,   135 
Treatment,  72 

,,  by  lumbar  puncture  alone,  75,  76,  81 

„  failure  of  early  forms  of,  73 

„  „       of  serum  in  1915,  76 

„  general,  85 

„  of  cases,  precautions  in,  130 

„  prognostic  value  of  date  of,  68;  78 

Trismus,  22 

Troops,  virulence  of  epidemics  among,  128 
Typhoid  fever,  differential  diagnosis  from,  35 
Typhus,  differential  diagnosis  from,  36 

Unconsciousness  at  onset,  13 

„  „  value  in  prognosis,  67 

United  Kingdom,  second  epidemic  wave  in,  6 
fifth  „  „         9 

United  States,  first 

„       second 

third  „  „  7 

fifth  „  „         9 

Urine,  disinfection  of,  132 
,,  incontinence  of,  20 
,,  ,,  in  acute  fatal  type,  46 

„       presence -of  meningococcus  m,  92,  118 
,,       retention  of.  in  acute  fatal  type,  46 
„  „  ,,        type  with  recovery,  48 

„  „  in  early  stage,  20 

,,  „  in  fulminating  type,  42 

„  „  ■  in  hydrocephalus,  55 

,,  ,,  value  in  diagnosis,  29 

Urotropin,  86  , 

Vaccination,  protective,  84 

Vaccine  treatment,  83 

Vaso-motor  changes,  24 

Vedder's  medium,  150 

Veins  of  eye,  fullness  of,  24 

Venesection  in  earlier  methods  of  treatment,  72 

Ventilation,  necessity  of  free,  85 

„  „  „        in  treatment,  131 

Ventricles,  cerebral,  in  acute  fatal  type,  99 
„  „  in  hydrocephalus,  101 

,,  „  operation  for  tapping,  88 

Vibices,  19 

Vines'  sugar  medium,  159 
Virulence,  high  among  troops,  128 

„  low,  under  normal  conditions,  91 

VitaUty  not  corresponding  to  staining  power,  141 

„        of  gram-negative  cocci,  143 

„         of  meningococcus,  151 

„         on  swabs,  136 
Vomiting  at  onset,  13,  14 


'222  General  Index 

Vomiting  in  acute  fatal  type,  44 

„  „      type  with  recovery,  47 

„  in  fulminating  type,  41 

„  in  hydrocephalus,  56 

,,  in  posterior  basic  meningitis,  60 

„  indication  for  puncture,  82 

,,  on  first  day,  64 

Wasting,  in  acute  stage,  25 

„         in  hydrocephalus,  56,  102 

„         in  posterior  basic  meningitis,  60 
Weather  conditions,  seasonal,  effect  on  susceptibility,  126 
West  Africa,  epidemic  in,  10 
West's  covered  swab,  133 
Winter,  cerebro-spinal  fever  a  disease  of,  129 

YeUow  cerebro-spinal  fluid.  111 


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Date 

Dise 

"^^^■w 

AHK  ib 

1942 

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d4S 

V 

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RC383«04 
Foster 


F81 


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